The Prognostic Value of Gross Tumor Volume in Early-Stage Extranodal NK/T-Cell Lymphoma Treated with Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Gross tumor volume (GTV) is a biological reflection of tumor burden. We aimed to evaluate the prognostic value of GTV in patients with early-stage extranodal NK/T-cell lymphoma (ENKTCL) treated with radiotherapy. <h3>Materials/Methods</h3> From 2003 to 2019, 326 patients with early-stage ENKTCL underwent intensive-modulated radiotherapy (IMRT) were reviewed retrospectively. GTV was computed using radiation therapy planning system. The association between GTV and death risk was flexibly modeled using smoothed restricted cubic splines. The optimal cutoff point of GTV was determined using receiver operating characteristics (ROC) curve. The overall survival (OS), progression-free survival (PFS), local failure-free survival (LFFS) and distant metastasis-free survival (DMFS) were estimated using Kaplan-Meier method and compared by log-rank test. Cox proportional hazards regression was performed to identify independent risk factors for OS, PFS, LFFS and DMFS. The inverse probability of treatment weighting (IPTW) was conducted to balance patients' characteristics between different subsets. <h3>Results</h3> With median follow-up time of 47.2 months, the 5-year OS, PFS, LFFS and DMFS for entire cohort were 63%, 72%, 92% and 76% respectively. Median GTV was 29.76 ml (ranging from 0.26 to 480.7 ml). GTV linearly correlated with OS. According to ROC curve, 35ml was identified as best cut-off value for OS (AUC = 0.71). Patients in higher GTV group were propensity to be characterized with Ann Arbor stage II, Eastern Cooperative Oncology Group (ECOG) performance score ≥2, B symptom, elevated lactate dehydrogenase and primary tumor invasion (PTI). Higher GTV was an independent risk factor for OS (HR = 2.4, 95%CI, 1.42-4.06, P = 0.001,) PFS (HR = 2.26, 95%CI, 1.44-3.53, P <0.001) and LFFS (P <0.001, HR = 3.79, 95%CI, 1.06-6.5), but not for DMFS (P = 0.1). The difference in OS was not significant (P = 0.084) after adjusting the confounding variables using IPTW. The negative correlation between GTV and LFFS can be attenuated by higher RT dose. <h3>Conclusion</h3> Higher GTV was a risk factor for multiple survival endpoints in early stage ENKTCL treated with radiotherapy. This study can help to provide the rational RT dose selection for different GTV.