Post-Hypofractionated Radiotherapy Neutrophil-to-Lymphocyte Ratio in Soft Tissue Sarcomas is a Prognostic Biomarker of Recurrence and Distant Metastases

Abstract

The neutrophil-to-lymphocyte ratio (NLR) is a measure of systemic inflammation, and known to be prognostic of outcomes and treatment response across different cancer types, including soft tissue sarcomas (STS). Our study aims to determine if in patients with STS treated with pre-operative hypofractionated radiotherapy (HFRT), post-RT NLR is prognostic of recurrence, metastasis, and overall survival. We performed a single-center retrospective analysis of patients treated pre-operatively with 30 Gy in 5 fractions between 2016 and 2023. Clinical, demographic, radiation therapy (RT), and complete blood count (CBC) data were collected from medical records. The NLR calculation was performed by dividing the absolute neutrophils count by the absolute lymphocytes count. We dichotomized the variable into NLR ≤4 and >4. The CBC utilized to calculate NLR was only used if done <6 months post-RT. For post-RT NLR outcomes associations, we used univariable and multivariable logistic regression analyses adjusting for age, gender, tumor size, and histology. For continuous variables we used mean ± standard deviation. Analyses were done with SPSS. A p-value <0.05 was considered significant. We identified 40 patients that received HFRT and had a CBC within 6 months after RT. The mean age was 66 ± 17.5 years. There were 17 (42.5%) females and 23 (57.5%) males. The histologies were myxofibrosarcoma (17.5%), leiomyosarcoma (7.5%), pleomorphic spindle cell sarcoma (10%), myxoid liposarcoma (5%). Other histologies with n<2 accounted for 65%. The mean tumor size was 7.1cm (± 6.4) and the mean NLR 5.3 ± 0.6. The median follow-up was 15.4 ±2.2 months. The patients with recurrence and metastases were the same {n = 13 (32.5%)}, and 3 patients died of disease. Univariable analyses for NLR > 4 showed increased recurrence and metastases (Odds ratio (OR): 8, CI 95% = {1.48 - 43.4}, p = 0.016). The multivariable analyses also showed that post-RT NLR > 4, was associated with increased recurrence and metastases (OR: 7.73, CI 95% = {1.17- 50.9}, p- value = 0.034). Age, gender, histology, and tumor size were not significant variables (Table 1). In both univariable and multivariable analyses NLR > 4 was not associated with decreased overall survival (p = 0.998). To our knowledge, this is the first study assessing the immune response using neutrophil-to-lymphocyte ratio as a prognostic biomarker in STS treated with pre-operative hypofractionated radiotherapy. In this population, an NLR > 4 was prognostic for recurrence and distant metastasis, but not for overall survival. This study highlights the need for a better understanding of the immuno-biological effects of RT, which should be further addressed in the context of clinical trials due to its simplicity and potential prognostic value.