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Because non-anthracycline-based chemotherapy with l-asparaginase has improved survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTL), the incidence of central nerve system (CNS) relapse can be different when compared with that in previous reports. In this research, we sought to identify the incidence of and predictors for CNS relapse and to evaluate the necessity of CNS prophylaxis with intermediate-dose methotrexate (ID-MTX). The records of 399 patients in the training cohort and 253 patients in the validation cohort with ENKTL who received non-anthracycline-based chemotherapy were reviewed. Patients were divided into 2 groups according to whether the chemotherapy regimen included ID-MTX above 2 g/m2. A new central nervous system-prognostic index of natural killer (CNS-PINK) model was developed using 1-point powerful predictors of CNS relapse (PINK; hazard ratio [HR], 2.908; P = .030 and extranodal involvement [≥2]; HR, 4.161; P = .001) and was calculated as a sum of scores. The high-risk group of CNS-PINK was defined as 2 points. The cumulative incidence of CNS relapse was different between the CNS-PINK risk groups in the training (P < .001) and validation (P = .038) cohorts. Patients in the high-risk CNS-PINK group who were treated with SMILE or SMILE-like regimens with ID-MTX (S-ID-MTX) displayed a lower incidence rate of CNS relapse than did those who received other regimens without ID-MTX in the training cohort (P = .029). The CNS-PINK was demonstrated its strong predictability of CNS relapse in ENKTL patients. The effectiveness of S-ID-MTX in preventing CNS events in high-risk CNS-PINK patients should be verified in future studies., (© 2020 by The American Society of Hematology.)

Objectives: To perform a systematic review of 1762 patients to comprehensively assess the benefit of altered-fractionation radiotherapy (ART) in early stage glottic carcinoma (ESGC)., Materials and Methods: Studies were identified in PubMed and EMBASE. Inclusion criteria were: (1) diagnosis of squamous cell ESGC (Tis, T1, T2); (2) ART versus conventionally-fractionationated radiotherapy (CRT); and (3) provision of number of local recurrence events and total numbers per fractionation arm. The random-effects model was fitted to estimate the pooled hazard ratio (HR). Subgroup sensitivity analyses were performed based on ART strategy (hypo- versus hyperfractionation), treatment-day reductions, machine type, tumor stage, and anterior commissure involvement., Results: Eleven studies met inclusion criteria: 4 randomized controlled trials (RCTs) and 7 two-arm retrospective studies. ART was associated with 38% fewer (HR 0.62; 95% CI: 0.46-0.82, p = 0.0009) and 60% fewer (HR 0.40; 95% CI: 0.24-0.66, p = 0.0003) local failure events in pooled analyses of the RCTs and retrospective studies, respectively. Both hyperfractionation (HR 0.65; 95% CI: 0.43-0.97, p = 0.03) and hypofractionation (HR 0.55; 95% CI: 0.33-0.91, p = 0.02) strategies were superior to CRT. The benefit persisted for all treatment- and tumor-related parameters, including anterior commissure involvement, with the exception of a pooled analysis of studies with predominantly T2 (<50% T1) cases (HR 0.60, 95% CI: 0.30-1.20, p = 0.15)., Conclusion: Both hypofractionation and hyperfractionation improve local control in ESGC, including T1 tumors and for anterior commissure involvement. However, this benefit may not persist for T2 tumors, for which alternative strategies should be considered., (Copyright © 2019 Elsevier Ltd. All rights reserved.)