Early-Stage Extranodal NK/T-cell Lymphoma: A Role for Elective Nodal Irradiation?

Abstract

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL) is rare in Western populations. We examined our institutional experience treating early-stage ENKTCL patients to elucidate patterns of failure and optimal treatment strategies for this aggressive disease. Between 1994 and 2015, we identified 41 patients treated at a single institution in the United States with pathologically-confirmed Ann-Arbor stage I or II ENKTCL. Endpoints analyzed included overall survival (OS), disease-specific survival (DSS), and local control (LC). Median age at diagnosis was 45 years (range 18 – 80 years). Thirty patients (73%) presented with stage I disease, and 11 (27%) with stage II disease. All patients had primary lesions of the upper aerodigestive tract; 39 patients (95%) had primary nasal disease. Definitive treatment included combined modality therapy (CMT) with chemotherapy (ChT) and radiotherapy (RT) in 33 patients (80%), RT alone in 7 (17%), and ChT alone in 1 (2%). Of the 33 patients treated with CMT, 18 (55%) received ChT followed by RT, 13 (39%) received RT followed by ChT, and 2 (6%) received concurrent ChT and RT. Median RT dose to the primary tumor was 50Gy (interquartile range 45 – 52.3Gy). Elective nodal irradiation (ENI) of draining lymphatics was performed in 9 patients (22%), of whom 6 had stage I disease; the 3 stage II patients treated with ENI had initial nodal disease involving ipsilateral levels IB and/or II, and were treated with ENI to ipsilateral levels III and IV, as well as contralateral cervical basins. No patients were treated with asparaginase-containing ChT regimens. Median follow-up for the cohort was 73 months. Two-year OS and DSS for the cohort were 74% and 63%, respectively. Nineteen patients (46%) experienced disease relapse, including 6 isolated local relapses, 6 isolated regional nodal relapses, 6 distant relapses, and 1 concurrent local and distant relapse. All 6 regional nodal relapses occurred in patients who had not received ENI (19% nodal failure rate for patients not treated with ENI). Moreover, 5 of 6 nodal relapses (83%) occurred in first-echelon draining lymph nodes relative to the primary tumor. ENI was associated with improved DSS (hazard ratio [HR] 0.34, 95% confidence interval [CI] 0.12 – 0.97, p=0.043). There was a trend toward improved LC with both RT dose to the primary tumor ≥50Gy (HR 0.27, CI 0.06 – 1.21, p=0.086) and RT first in the treatment sequence (HR 0.24, CI 0.05 – 1.04, p=0.057). With disease-related outcomes comparable to previously-reported data from Asia, this Western cohort of early-stage ENKTCL patients highlights a potential benefit to ENI in the setting of non-asparaginase-containing CMT. This is supported by high rates of nodal failure in first-echelon nodal stations relative to the primary tumor. Additionally, RT dose ≥50Gy to the primary tumor and first-line RT delivery in the setting of non-asparaginase-containing CMT should be considered.