Clinical impact of lymphatic spread in patients with limited-stage upper aerodigestive tract NK/T cell lymphoma

Moo-Kon Song; Joo-Seop Chung; Sung-Yong Oh; Sung-Nam Lim; Won-Sik Lee; Sang-Min Lee; Do-Young Kim

doi:10.5045/br.2021.2020328

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Original Article

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Blood Res 2021; 56(2):

Published online June 30, 2021

https://doi.org/10.5045/br.2021.2020328

Clinical impact of lymphatic spread in patients with limited-stage upper aerodigestive tract NK/T cell lymphoma

Moo-Kon Song¹, Joo-Seop Chung², Sung-Yong Oh³, Sung-Nam Lim⁴, Won-Sik Lee⁵, Sang-Min Lee⁵, Do-Young Kim²

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¹Department of Hematology, Hanyang University Hanmaeum Changwon Hospital, Changwon, ²Department of Hematology-Oncology, Pusan National University Hospital Medical Research Institute, ³Department of Oncology, Dong-A University Hospital, ⁴Department of Hematology, Busan Haeundae Paik Hospital, ⁵Department of Hematology, Busan Paik Hospital, Busan, Korea

Correspondence to : Joo-Seop Chung, M.D., Ph.D.
Department of Hematology-Oncology, School of Medicine, Pusan National University, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea
E-mail: hemon@pusan.ac.kr

Received: December 21, 2020; Revised: March 1, 2021; Accepted: March 19, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Background
We investigated whether distance_max, that is, the degree of distance between the upper aerodigestive tract (UAT) mass and the farthest pathologic lymph node, was significantly associated with survival in patients with limited-stage UAT natural killer/T cell lymphoma (NKTCL).
Methods
A total of 157 patients who received chemotherapy (CTx) with/without radiotherapy (RTx) were enrolled.
Results
In the survival analysis, an elevated lactate dehydrogenase level [progression-free survival (PFS): hazard ratio (HR), 2.948; 95% confidence interval (CI), 1.606‒5.404; P <0.001; overall survival (OS): HR, 2.619; 95% CI, 1.594‒4.822; P =0.003], short distance_max (PFS: HR, 0.170; 95% CI, 0.071‒0.410; P <0.001; OS: HR, 0.142; 95% CI, 0.050‒0.402; P < 0.001), and CTx combined with RTx (HR, 0.168; 95%CI, 0.079‒0.380; P <0.001; OS: HR, 0.193; 95% CI, 0.087‒0.429; P <0.001) had an independent predictive value for PFS and OS.
Conclusion
The evaluation of the degree of lymphatic spread and local control by CTx combined with RTx is essential in patients with limited-stage UAT NKTCL.

Keywords Upper aerodigestive tract, Radiotherapy, Natural killer/T cell lymphoma

Article

Original Article

Blood Res 2021; 56(2): 72-78

Published online June 30, 2021 https://doi.org/10.5045/br.2021.2020328

Clinical impact of lymphatic spread in patients with limited-stage upper aerodigestive tract NK/T cell lymphoma

Moo-Kon Song¹, Joo-Seop Chung², Sung-Yong Oh³, Sung-Nam Lim⁴, Won-Sik Lee⁵, Sang-Min Lee⁵, Do-Young Kim²

Correspondence to:Joo-Seop Chung, M.D., Ph.D.
Department of Hematology-Oncology, School of Medicine, Pusan National University, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea
E-mail: hemon@pusan.ac.kr

Received: December 21, 2020; Revised: March 1, 2021; Accepted: March 19, 2021

Abstract

Keywords: Upper aerodigestive tract, Radiotherapy, Natural killer/T cell lymphoma

Abstract

Fig 1.

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Figure 1.Receiver operating characteristic (ROC) curves to identify optimal cutoff value of maximum distance (distance_max) from primary extra nodal site to the farthest lymph node, and maximum standard uptake value (SUV_max) in patients with limited stage upper aerodigestive tract natural killer/T cell lymphoma. The calculated optimal cutoffs for distance_max and SUV_max were 10.8 and 7.1 respectively. In addition, the area under the ROC curve (AUC) values for distance_max and SUV_max were 0.874 and 0.632, respectively. The AUC value for distance_max was significantly higher than that for SUV_max (P<0.001).

Blood Research 2021; 56: 72-78https://doi.org/10.5045/br.2021.2020328

Fig 2.

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Figure 2.Survival analysis according to distance_max in patients with limited stage upper aerodigestive tract natural killer/T cell lymphoma. Differences in the short distance_max group (N=67) and long distance_max group (N=90) were significant (progression-free survival, P<0.001; Fig. 2A; OS, P<0.001; Fig. 2B).

Blood Research 2021; 56: 72-78https://doi.org/10.5045/br.2021.2020328

Fig 3.

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Figure 3.Prognosis according to degree of lymphatic spread and therapeutic modality. In the Kaplan-Meier survival curve, lymphoma involvement of short distance_max in patients treated with CTx and RTx had the most favorable PFS and OS (PFS, P<0.001; Fig. 3A; OS, P<0.001, Fig. 3B). Meanwhile, involvement of long distance_max in patients received only CTx had worst PFS and OS (PFS, P<0.001, Fig. 3A; OS, P<0.001, Fig. 3B). Lymphoma involvement of short distance_max in patients treated with only CTx and long distance_max involvement in patients who received chemotherapy combined with radiotherapy did not have significant survival differences (PFS, P=0.431; OS, P=0.578).

Blood Research 2021; 56: 72-78https://doi.org/10.5045/br.2021.2020328

Table 1 . Baseline characteristics of patients with limited stage natural killer/T cell lymphoma..

Characteristics	N (157)
Age
Median (range)	58 (37–78)
≥60 yr (%)	71 (45.2)
<60 yr (%)	86 (54.8)
Sex
Male (%)	108 (68.8)
Female (%)	49 (31.2)
Primary site
Nasal cavity (%)	117 (74.5)
Nasopharynx (%)	34 (21.7)
Oral cavity/oropharynx (%)	6 (3.8)
Ann-Arbor stage
Stage I	20 (12.7)
Stage II	137 (87.3)
Lactate dehydrogenase
≥Upper normal limit (%)	31 (19.7)
Normal (%)	126 (80.3)
Ki-67 value
≥70% (%)	25 (15.9)
<70% (%)	127 (84.1)
B symptoms
Present (%)	40 (25.5)
Absent (%)	117 (74.5)
ECOG performance status
Grade 0–1 (%)	114 (72.6)
≥Grade 2 (%)	43 (27.4)
Bulky disease (≥7.5 cm)
Present (%)	16 (10.2)
Absent (%)	141 (89.8)
Bilateral RLN involvement
Present (%)	35 (22.3)
Absent (%)	122 (87.7)
Therapeutic modality
Chemotherapy only (%)	81 (51.6)
Chemotherapy with radiotherapy (%)	76 (48.4)
18F-FDG PET/CT scan
SUV_max, median (range)	8.9 (2.7–41.0)

Abbreviations: 18F-FDG, 18F-fluorodeoxyglucose; ASCT, autologous stem cell transplantation; ECOG, Eastern Cooperative Oncology Group; PET/CT, positron emission tomography/computed tomo-graphy; RLN, regional lymph node; SUV_max, maximum standard uptake value..

Table 2 . Univariate and multivariate analysis of prognostic factors for survival in 157 patients with limited natural killer/T cell lymphoma, nasal type..

	Progression-free survival			Overall survival
	Univariate	Multivariate		Univariate	Multivariate
	P	HR (95% CI)	P	P	HR (95% CI)	P
Male sex	0.059	-	-	0.458	-	-
B symptoms	0.568	-	-	0.504	-	-
Age≥60 yr	0.015	0.928 (0.514–1.675)	0.804	0.011	0.943 (0.485–1.835)	0.863
Stage II	0.007	0.965 (0.466–1.999)	0.924	0.076	-	-
LDH>normal	<0.001	2.948 (1.606–5.404)	<0.001	0.009	2.619 (1.394–4.822)	0.003
ECOG PS≥grade 2	0.003	1.778 (0.959–3.288)	0.068	0.016	2.002 (0.991–4.043)	0.053
High Ki-67≥70	0.007	1.388 (0.769–2.507)	0.276	0.068	-	-
low SUV_max<7.1	<0.001	0.538 (0.258–1.126)	0.100	0.056	-	-
Regional LN involvement	0.034	0.627 (0.304–1.290)	0.205	0.386	-	-
Short distance_max	<0.001	0.170 (0.071–0.410)	<0.001	<0.001	0.142 (0.050–0.402)	<0.001
Bilateral LN involvement	<0.001	1.748 (0.980–3.112)	0.059	0.003	2.532 (0.984–4.713)	0.212
Bulky disease (≥7.5 cm)	0531	-	-	0.355	-	-
CTx combined with RTx	<0.001	0.168 (0.079–0.380)	<0.001	<0.001	0.193 (0.087–0.429)	<0.001

Abbreviations: CI, confidence interval; CTx, chemotherapy; distance_max, maximum distance length; ECOG, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IPI, International Prognostic index; RLN, regional lymph node; RTx, radiotherapy; SUV_max, maximum standard uptake value..