Oncotarget, Vol. 7, No. 47
www.impactjournals.com/oncotarget/
Clinical Research Paper
Body mass index as a prognostic factor in patients with extranodal natural killer/T-cell lymphoma, nasal type Jie Liu1, Yao-Tiao Deng1, Li Zhang1, Na Li1, Ming Jiang1, Li-Qun Zou1 and Yu Jiang1 1
Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China Correspondence to: Yu Jiang , email: [email protected] Correspondence to: Li-qun Zou , email: [email protected] Keywords: extranodal natural killer/T-cell lymphoma, body mass index, prognosis, radiotherapy, chemotherapy Received: May 10, 2016
Accepted: August 13, 2016
Published: August 18, 2016
ABSTRACT Epidemiological evidence has shown that body mass index (BMI) can predict survival in several types of cancer. However, the role of BMI in extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is still unclear. This retrospective singlecenter study included 251 newly diagnosed patients to determine the prognostic value of BMI in ENKTL. Of these, 203 patients received chemoradiotherapy, 37 received chemotherapy alone, 8 received radiotherapy alone, and 3 received only best supportive care. With a median follow-up of 28 months, the estimated 3-year overall survival (OS) and progression-free survival (PFS) rates were 64.4% and 60.9%, respectively. The receiver-operating characteristic curve showed that 20.8 kg/m2 was the optimal cut-off of BMI to predict survival. BMI < 20.8 kg/m2 was associated with lower 3-year OS (52.8% vs. 72.9%, P = 0.001) and PFS (48.8% vs. 69.8%, P < 0.001) rates. Multivariate analysis indicated that BMI, performance status, lactate dehydrogenase (LDH) levels, chemotherapy, and radiotherapy were independent prognostic factors for OS. Furthermore, BMI, number of extranodal sites, performance status, LDH, and radiotherapy were predictive of PFS. These results suggest that BMI at the cut-off of 20.8 kg/m2 might be a prognostic factor in patients with ENKTL.
INTRODUCTION
survival of ENKTL patients has improved owing to early radiotherapy and new chemotherapy regimens containing asparaginase and other non-anthracycline drugs [2, 4-10]. The prognostic index of natural killer lymphoma (PINK) model published in 2016 was developed for patients who received non-anthracycline-based chemotherapy with or without radiotherapy, based on their clinical characteristics including age, stage, distant lymph node (DLN) involvement, and non-nasal type disease [11]. Body mass index (BMI) is one of the common criteria to evaluate the degree of obesity. Increased BMI is associated with a higher risk of diabetes mellitus, cardiovascular diseases [12], as well as cancers [13]. Recent evidence has also shown that abnormal BMI can predict prognosis in many types of cancers [14-23], such as breast [14], colon [15] and liver [22] cancers, and diffuse large B-cell lymphoma (DLBCL) [17-19]. Although there is sufficient evidence in these cancers, the role of BMI in ENKTL is still unclear. Therefore, we carried out this retrospective study to determine the
Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a rare subset of non-Hodgkin’s lymphoma (NHL). It is more frequent in Asia and Latin America, accounting for 7%-10% of all NHLs in these areas, but only 1% in western countries [1]. ENKTL can be dichotomized as nasal disease primarily localized to the upper aerodigestive tract (UAT), or extranasal disease occurring in non-UAT sites (e.g., skin, intestine, testicles) [2]. According to the data from the International Peripheral T-Cell Lymphoma Project, the median overall survival (OS) was only 0.36 and 1.6 years for extranasal and nasal disease, respectively [2]. In 2006, Lee et al. established a prognostic model for ENKTL, known as the Korean Prognostic Index, which contained four factors: B symptoms, serum lactate dehydrogenase (LDH) level, stage, and regional lymph node (RLN) involvement [3]. In this study, most patients (202/262) had received anthracycline-based chemotherapy [3]. Recently, the www.impactjournals.com/oncotarget
78159
Oncotarget
prognostic value of BMI in newly diagnosed patients with ENKTL.
classification. Most (n = 203, 80.9%) patients received chemoradiotherapy, 37 (14.7%) received chemotherapy alone, 8 (3.2%) received radiotherapy alone, and 3 (1.2%) received only best supportive care. The chemotherapy regimens included VDLP (etoposide, dexamethasone, L-asparaginase, and cisplatin: 184 patients), LVP (L-asparaginase, vincristine, and prednisone: 36 patients), asparaginase combined with non-anthracycline drugs (e.g., gemcitabine, irinotecan, or dexamethasone: 8 patients), CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisone: 8 patients), and other regimens in 4 patients. Of patients treated with radiotherapy, 205 (97.2%) completed the planned dose (50-56 Gy). By December 2015, 79 patients had died. The median follow-up time was 28 months (range, 8-86 months) for patients who were alive. The estimated 3-year OS and PFS rates were 64.4% and 60.9%, respectively. Patient characteristics are listed in Table 1.
RESULTS Patient characteristics In total, 301 patients met the inclusion criteria. Fifty cases were excluded. Of these, 28 patients had primary extranasal diseases, 9 were younger than 18 years, 6 were complicated by other types of cancer, and the staging was unclear in 7 patients. The median age of the remaining 251 eligible patients was 42 years (range, 18-86 years), and 170 (67.7%) patients were male. At diagnosis, 40 patients (15.9%) were classified as underweight, 130 (51.8%) as normal weight, 49 (19.6%) as overweight, and 32 (12.7%) as obese according to the Asian criteria of BMI
Figure 1: Survival curves of 251 patients diagnosed with ENKTL. A. and B. Patients were stratified into BMI groups according to the Asian criteria: underweight ( < 18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23.0-24.9 kg/m2) and obese ( ≥ 25.0 kg/ m2). C. and D. Patients were divided by the optimal cut-off of BMI (20.8 kg/m2). www.impactjournals.com/oncotarget
78160
Oncotarget
Table 1: Patient characteristics Characteristic
No. of patients
%
Characteristic
Gender
No. of patients
%
Ann Arbor Stage
Female
81
32.3%
I–II
213
84.9%
Male
170
67.7%
III–IV
38
15.1%
Age
Local invasiveness
≤60
219
87.3%
No
178
70.9%
>60
32
12.7%
Yes
73
29.1%
B symptoms
RLN involvement
No
122
48.6%
No
164
65.3%
Yes
129
51.4%
Yes
87
34.7%
Performance status
DLN involvement
0-1
223
88.8%
No
236
94.0%
2-4
28
11.2%
Yes
15
6.0%
LDH
No. of extranodal sites
Normal
151
60.2%
1 site
216
86.1%
Elevated
100
39.8%
>1 site
35
13.9%
40 211
15.9% 84.1%
228 12 11
90.8% 4.8% 4.4%
BMI
www.impactjournals.com/oncotarget/
Clinical Research Paper
Body mass index as a prognostic factor in patients with extranodal natural killer/T-cell lymphoma, nasal type Jie Liu1, Yao-Tiao Deng1, Li Zhang1, Na Li1, Ming Jiang1, Li-Qun Zou1 and Yu Jiang1 1
Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China Correspondence to: Yu Jiang , email: [email protected] Correspondence to: Li-qun Zou , email: [email protected] Keywords: extranodal natural killer/T-cell lymphoma, body mass index, prognosis, radiotherapy, chemotherapy Received: May 10, 2016
Accepted: August 13, 2016
Published: August 18, 2016
ABSTRACT Epidemiological evidence has shown that body mass index (BMI) can predict survival in several types of cancer. However, the role of BMI in extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is still unclear. This retrospective singlecenter study included 251 newly diagnosed patients to determine the prognostic value of BMI in ENKTL. Of these, 203 patients received chemoradiotherapy, 37 received chemotherapy alone, 8 received radiotherapy alone, and 3 received only best supportive care. With a median follow-up of 28 months, the estimated 3-year overall survival (OS) and progression-free survival (PFS) rates were 64.4% and 60.9%, respectively. The receiver-operating characteristic curve showed that 20.8 kg/m2 was the optimal cut-off of BMI to predict survival. BMI < 20.8 kg/m2 was associated with lower 3-year OS (52.8% vs. 72.9%, P = 0.001) and PFS (48.8% vs. 69.8%, P < 0.001) rates. Multivariate analysis indicated that BMI, performance status, lactate dehydrogenase (LDH) levels, chemotherapy, and radiotherapy were independent prognostic factors for OS. Furthermore, BMI, number of extranodal sites, performance status, LDH, and radiotherapy were predictive of PFS. These results suggest that BMI at the cut-off of 20.8 kg/m2 might be a prognostic factor in patients with ENKTL.
INTRODUCTION
survival of ENKTL patients has improved owing to early radiotherapy and new chemotherapy regimens containing asparaginase and other non-anthracycline drugs [2, 4-10]. The prognostic index of natural killer lymphoma (PINK) model published in 2016 was developed for patients who received non-anthracycline-based chemotherapy with or without radiotherapy, based on their clinical characteristics including age, stage, distant lymph node (DLN) involvement, and non-nasal type disease [11]. Body mass index (BMI) is one of the common criteria to evaluate the degree of obesity. Increased BMI is associated with a higher risk of diabetes mellitus, cardiovascular diseases [12], as well as cancers [13]. Recent evidence has also shown that abnormal BMI can predict prognosis in many types of cancers [14-23], such as breast [14], colon [15] and liver [22] cancers, and diffuse large B-cell lymphoma (DLBCL) [17-19]. Although there is sufficient evidence in these cancers, the role of BMI in ENKTL is still unclear. Therefore, we carried out this retrospective study to determine the
Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a rare subset of non-Hodgkin’s lymphoma (NHL). It is more frequent in Asia and Latin America, accounting for 7%-10% of all NHLs in these areas, but only 1% in western countries [1]. ENKTL can be dichotomized as nasal disease primarily localized to the upper aerodigestive tract (UAT), or extranasal disease occurring in non-UAT sites (e.g., skin, intestine, testicles) [2]. According to the data from the International Peripheral T-Cell Lymphoma Project, the median overall survival (OS) was only 0.36 and 1.6 years for extranasal and nasal disease, respectively [2]. In 2006, Lee et al. established a prognostic model for ENKTL, known as the Korean Prognostic Index, which contained four factors: B symptoms, serum lactate dehydrogenase (LDH) level, stage, and regional lymph node (RLN) involvement [3]. In this study, most patients (202/262) had received anthracycline-based chemotherapy [3]. Recently, the www.impactjournals.com/oncotarget
78159
Oncotarget
prognostic value of BMI in newly diagnosed patients with ENKTL.
classification. Most (n = 203, 80.9%) patients received chemoradiotherapy, 37 (14.7%) received chemotherapy alone, 8 (3.2%) received radiotherapy alone, and 3 (1.2%) received only best supportive care. The chemotherapy regimens included VDLP (etoposide, dexamethasone, L-asparaginase, and cisplatin: 184 patients), LVP (L-asparaginase, vincristine, and prednisone: 36 patients), asparaginase combined with non-anthracycline drugs (e.g., gemcitabine, irinotecan, or dexamethasone: 8 patients), CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisone: 8 patients), and other regimens in 4 patients. Of patients treated with radiotherapy, 205 (97.2%) completed the planned dose (50-56 Gy). By December 2015, 79 patients had died. The median follow-up time was 28 months (range, 8-86 months) for patients who were alive. The estimated 3-year OS and PFS rates were 64.4% and 60.9%, respectively. Patient characteristics are listed in Table 1.
RESULTS Patient characteristics In total, 301 patients met the inclusion criteria. Fifty cases were excluded. Of these, 28 patients had primary extranasal diseases, 9 were younger than 18 years, 6 were complicated by other types of cancer, and the staging was unclear in 7 patients. The median age of the remaining 251 eligible patients was 42 years (range, 18-86 years), and 170 (67.7%) patients were male. At diagnosis, 40 patients (15.9%) were classified as underweight, 130 (51.8%) as normal weight, 49 (19.6%) as overweight, and 32 (12.7%) as obese according to the Asian criteria of BMI
Figure 1: Survival curves of 251 patients diagnosed with ENKTL. A. and B. Patients were stratified into BMI groups according to the Asian criteria: underweight ( < 18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23.0-24.9 kg/m2) and obese ( ≥ 25.0 kg/ m2). C. and D. Patients were divided by the optimal cut-off of BMI (20.8 kg/m2). www.impactjournals.com/oncotarget
78160
Oncotarget
Table 1: Patient characteristics Characteristic
No. of patients
%
Characteristic
Gender
No. of patients
%
Ann Arbor Stage
Female
81
32.3%
I–II
213
84.9%
Male
170
67.7%
III–IV
38
15.1%
Age
Local invasiveness
≤60
219
87.3%
No
178
70.9%
>60
32
12.7%
Yes
73
29.1%
B symptoms
RLN involvement
No
122
48.6%
No
164
65.3%
Yes
129
51.4%
Yes
87
34.7%
Performance status
DLN involvement
0-1
223
88.8%
No
236
94.0%
2-4
28
11.2%
Yes
15
6.0%
LDH
No. of extranodal sites
Normal
151
60.2%
1 site
216
86.1%
Elevated
100
39.8%
>1 site
35
13.9%
40 211
15.9% 84.1%
228 12 11
90.8% 4.8% 4.4%
BMI
