Primary site and regional lymph node involvement are independent prognostic factors for early-stage extranodal nasal-type natural killer/T cell lymphoma

Abstract

Background: Nasal-type extranodal natural killer/T-cell lymphoma (ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract. However, it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement. The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL.

Methods: To develop a nomogram, we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C-index) and calibration curve.

Results: The 5-year overall survival (OS) and progression-free survival (PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL (OS: 68.2% vs. 46.0%, P = 0.030; PFS: 53.4% vs. 26.6%, P = 0.010). The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage IIE ENKTCL (OS: 66.3% vs. 59.2%, P = 0.003; PFS: 51.4% vs. 40.3%, P = 0.009). Multivariate analysis showed that age >60 years, ECOG performance status score ≥2, elevated lactate dehydrogenase (LDH) level, extra-nasal primary site, and regional lymph node involvement were significantly associated with lower 5-year OS rate; age >60 years, elevated LDH level, extra-nasal primary site, and regional lymph node involvement were significantly associated with lower 5-year PFS rate. The nomogram included the primary site and regional lymph node involvement based on multivariate analysis. The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates, and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634, respectively.

Conclusions: The primary site and regional lymph node involvement are independent prognostic factors for early-stage ENKTCL treated with chemotherapy followed by definitive radiotherapy.

Keywords: Extranodal natural killer/T-cell lymphoma (ENKTCL); Lymph node; Nasal cavity; Nomogram; Prognosis.

Fig. 1

Overall survival (OS) and progression-free survival (PFS) of 215 patients with early-stage nasal-type extranodal natural killer/T-cell lymphoma (ENKTCL)

Fig. 2

Kaplan-Meier OS and PFS curves for patients with ENKTCL categorized by primary site and regional lymph node involvement. a OS curves for patients with nasal and extra-nasal disease; b OS curves for patients with Ann Arbor stage IIE or IE disease (i.e., with or without regional lymph node involvement); c PFS curves for patients with nasal and extra-nasal disease; d PFS curves for patients with Ann Arbor stage IE or IIE disease

Fig. 3

Survival curves for patients with nasal and extra-nasal ENKTCL at Ann Arbor stage IE and IIE. a OS for patients with nasal and extra-nasal disease at Ann Arbor stage IE; b PFS for patients with nasal and extra-nasal disease at Ann Arbor stage IE; c OS for patients with nasal and extra-nasal disease at Ann Arbor stage IIE; d PFS for patients with nasal and extra-nasal disease at Ann Arbor stage IIE

Fig. 4

A nomogram for patients with early-stage upper aerodigestive tract natural killer/T-cell lymphoma. To use the nomogram, an individual patient’s value is located on each variable axis, and a line is drawn upward to determine the number of points received for each variable value. The sum of these numbers is located on the total points axis, and a line is drawn downward to the survival axes to determine the likelihood of 5-year OS (a) and PFS (b) rates. Site primary site of the lymphoma, LDH pretreatment level of serum lactate dehydrogenase, ECOG eastern cooperative oncology group, LN regional lymph node

Fig. 5

Internal validation of the nomogram used to predict OS and PFS in patients with upper aerodigestive tract nasal-type extranodal natural killer/T-cell lymphoma. Discrimination and Calibration: Calibration plot for predicting 5-year OS rate (a) and 5-year PFS rate (b). The areas under the receiver operating characteristic curve are 0.697 for 5-year OS rate (c) and 0.634 for 5-year PFS rate (d). The nomogram-predicted survival is plotted on the X axis; the actual survival is plotted on the Y axis. AUC area under the curve