Treatment Outcomes of Early-Stage Natural-Killer/T-Cell Lymphomas Treated with Chemoradiotherapy: Data from 3 Tertiary Cancer Centres in Singapore

Background: Extranodal natural killer/T cell lymphoma (ENKL) is an aggressive Epstein-Barr virus (EBV) associated lymphoma with a strong geographical predilection for Asia and South America. While treatment outcomes of advanced stage (AS) disease (i.e., stage III and IV) are uniformly poor, early stage (ES) disease treated with concomitant or sequential chemotherapy (ChT) and radiotherapy (RT) can yield good long-term outcomes. Currently there is no standard therapy for ES ENKL. We describe our experience treating patients with ES ENKL in 3 tertiary cancer centres in Singapore. Method: We performed a retrospective analysis using data from Singapore Lymphoma Study Group database which captures patients from 3 largest tertiary cancer centres in Singapore: National Cancer Centre Singapore (NCCS), Singapore General Hospital (SGH) and National University Cancer Institute, Singapore (NCIS). We included patients with stage I or II ENKL that were treated with ChT and RT from 1996 to March 2019. Patients who did not receive treatment or received radiotherapy alone were excluded. We recorded data on patient demographics, chemotherapy regimen, radiotherapy dosage, sequencing of treatment, response and survival outcomes. End of treatment overall response rates (ORR) included those who achieved complete response (CR) and a partial response (PR). Progression free survival (PFS) was defined as date of diagnosis to date of progression, relapse or death. Overall survival (OS) was defined as date of diagnosis to date of death from all causes. Survival distributions were estimated by the Kaplan-Meier method. Assuming cox proportional hazards models, univariate analysis for OS was performed and Wald tests were used to evaluate the statistical significance. All the statistical analysis was performed using R. Results: There were 56 patients who fulfilled the inclusion criteria. Forty (71%) were male, 47 (84%) were Chinese and the median age of this cohort was 50 (range 18-80). Thirty-one (55%) patients had stage I disease and all had nasal involvement. All patients had ECOG performance status of 0 or 1 and most had low or low-intermediate international prognostic index (IPI) score. Ten patients (18%) had B-symptoms and LDH was elevated in 22 (39%). Pre-treatment positron emission tomography-computed tomography (PET/CT) was performed in 36 (64%) patients. Pre-treatment EBV titres were tested in only 23 patients and they were detected in 17 (74%) of patients. Twenty-five patients