The prognostic value of lactate dehydrogenase/albumin ratio in extranodal natural killer/T cell lymphoma

The prognostic value of lactate dehydrogenase/albumin ratio in extranodal natural killer/T cell lymphoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The prognostic value of lactate dehydrogenase/albumin ratio in extranodal natural killer/T cell lymphoma Na Li, You Feng, Xin Chen, Li-qun Zou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5503269/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Jul, 2025 Read the published version in BMC Cancer → Version 1 posted 8 You are reading this latest preprint version Abstract Objective Extranodal natural killer/T-cell lymphoma (ENKTL) is recognized for its aggressive nature and variable clinical presentation, often leading to a poor prognosis. While the combined assessment of baseline serum lactate dehydrogenase (LDH) and albumin (ALB) levels has demonstrated prognostic value across various malignancies, its specific application and evidence in ENKTL are unstudied. Purpose This study aimed to investigate the impact of the lactate dehydrogenase/albumin ratio (LAR) in ENKTL, offering nutritional and immunological insights to enhance risk stratification. Results We conducted a retrospective analysis of 484 ENKTL patients treated with asparaginase-based regimens. The optimal thresholds for serum LDH and ALB levels were identified as 230 u/L and 40 g/L, respectively, and 5.4 for LAR. With a median follow-up of 70 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were determined to be 58.7% and 52.0%, respectively. Patients with higher LAR values exhibited more unfavorable clinical features and poorer 5-year OS and PFS rates compared to those with lower LAR values. Utilizing the LAR-associated prognostic score, patients were categorized into distinct risk groups, revealing significant differences in 5-year OS and PFS among these groups. By integrating the LAR and LAR-associated prognostic score into the prognostic index for natural killer lymphoma (PINK) and PINK with Epstein-Barr virus (PINK-E) models, we found that these measures provided additional prognostic information. Conclusion Elevated LDH and decreased ALB levels at the time of initial diagnosis are indicative of a poor prognosis in ENKTL patients. The LAR and LAR-associated prognostic score may serve as independent prognostic indicators for ENKTL, potentially aiding in risk stratification and informing clinical decision-making. Extranodal natural killer/T-cell lymphoma lactate dehydrogenase albumin lactate dehydrogenase/albumin ratio prognosis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Extranodal natural killer/T-cell lymphoma (ENKTL) represents a heterogeneous disease with a predominant manifestation in the nasal cavity and nasopharynx, exhibiting a strong association with Epstein-Barr virus (EBV) infection [ 1 ] . Approximately 10–20% of these lymphomas arise in locations outside the nasal cavity, including the skin, testes, gastrointestinal tract, muscle, and salivary glands [ 2 ] . ENKTL is more prevalent in Asia and, to a lesser degree, in Latin America, while it is considered rare in European and North American. ENKTL cells exhibit elevated levels of P-glycoprotein, which confers resistance to anthracycline-based therapies [ 3 ] . Given the enhanced survival outcomes observed in patients with ENKTL, treatment protocols incorporating asparaginase are currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines [ 4 ] . However, despite the advances, a significant number of patients still relapse and become refractory, leading to an unsatisfactory prognosis [ 5 – 7 ] . Identifying and confirming the clinical risk factors in patients with ENKTL can enhance the accuracy of prognosis by enabling more precise stratification, and in turn, offer valuable insights to guide clinical treatment decisions. The International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) models were developed in anthracycline-based era. However, utilizing these models, the survival for patients undergoing asparaginase-based therapies were not able to be precisely categorized [ 8 , 9 ] . The prognostic index for natural killer lymphoma (PINK) and PINK with Epstein-Barr virus (PINK-E) models have demonstrated validity in ENKTL, but they have not yet effectively identified risk categories for patients with early-stage disease [ 10 ] . Despite the nomogram-revised risk index (NRI) showing a higher predictive accuracy for overall survival (OS) when compared to the well-established IPI, KPI, PINK, and PINK-E models, it is crucial to recognize that these indices do not account for patients' comorbidities [ 11 ] . Malnutrition is prevalent among patients with malignancy, affecting approximately 80% of those in the advanced stages of their disease [ 12 ] . Despite a limited comprehension of the precise mechanisms behind nutritional alterations in malignancy, it is recognized that catabolic substances released by tumor cells, in conjunction with the host's inflammatory reactions, can lead to increased energy expenditure. This can cause a reduction in body weight and may culminate in malnutrition [ 13 ] . As the predominant plasma protein, serum albumin (ALB) offers a readily measurable indicator. Extensively utilized in clinical settings, it serves as a vital component in the prognostic evaluation of a variety of medical conditions [ 14 ] . Tumor cells exhibit increased metabolic activity, characterized by elevated glucose consumption and lactate output. Lactate dehydrogenase (LDH) is a marker that is conveniently and routinely measured in patients with malignancy, providing insights into the tumor load. Increased levels of LDH, serving as an adverse prognostic indicator, facilitate the suppression and evasion of the immune system by tumor cells through the modification of the tumor microenvironment [ 15 ] . Levels of ALB and LDH offer crucial insights into a patient's immune function, inflammatory activity, and tumor burden, establishing themselves as significant prognostic markers across various malignancies. Although previous studies have highlighted the prognostic relevance of the lactate dehydrogenase/albumin ratio (LAR) in colon cancer [ 16 ] , gastric cancer [ 17 ] , breast cancer [ 18 ] , and diffuse large B-cell lymphoma (DLBCL) [ 19 ] , its predictive value in ENKTL has not been reported. Therefore, we conducted a study to explore the predictive value of the LAR and LAR-associated prognostic score toward the prognosis of ENKTL patients receiving asparaginase-containing regimens. Materials and methods Patients Between January 2009 and January 2020, a retrospective review was conducted on 484 patients with ENKTL, extracted from medical records. The inclusion criteria were: (1) a pathological diagnosis of ENKTL without a history of prior antitumor treatments; (2) absence of any previous or concurrent malignancies; (3) chemotherapy regimens including L-asparaginase or pegaspargase, and (4) availability of comprehensive clinical, laboratory data, and follow-up details. Data collection Clinical data were collected as follows: age, gender, Eastern Cooperative Oncology Group (ECOG) performance status (PS), primary site of the lesion, regional lymph node invasion (RLN), distant lymph node invasion (DLN), extranodal invasion, bone marrow (BM) invasion, B symptoms, and Ann Arbor stage. Laboratory parameters including ALB levels, LDH concentrations, and EBV-DNA titer. A measurable level of EBV-DNA was considered positive due to the lack of a universally agreed-upon optimal cutoff value for EBV titer in predicting prognosis. Previous models including PINK (age, stage, non-nasal type, DLN) and PINK-E (age, stage, non-nasal type, DLN, and EBV-DNA status) were also used to enforce survival analysis. Pretreatment LAR was calculated as lactate dehydrogenase/albumin ratio. We proceeded to combine the categorized levels of LDH and ALB to generate the LAR-associated prognostic score, categorizing patients into three risk groups: low-risk (normal LDH and ALB levels), intermediate-risk (high LDH or low ALB levels), and high-risk (high LDH and low ALB levels) (Supplementary tabl e1 ). Treatment A total of 346 patients (71.5%) received chemoradiotherapy and 138 cases (28.5%) underwent chemotherapy. The chemotherapy regimens were formulated with either L-asparaginase or pegaspargase as their foundation and primarily included the following combinations: (1) LVDP (L-asparaginase 6000 IU/m2 intravenously on days 1–5, etoposide 80 mg/m2 intravenously on days 1–3, dexamethasone 40 mg/day intravenously on days 1–4, cisplatin 25 mg/m2 intravenously on days 1–3; repeated every 21 days); (2) LVP (L-asparaginase 5500 IU/m2 intravenously on days 1–5, vincristine 1.4 mg/m2 given intravenously on day 1, prednisone 100 mg orally on days 1–5; repeated every 21 days); (3) GLIED (gemcitabine 1000 mg/m2 intravenously on days 1, 8, L-asparaginase 6000 IU/m2 intravenously on days 4, 6, 8, 10, 12; ifosfamide 1000 mg/m2 intravenously on days 1–3; dexamethasone 20 mg intravenously on days 1–4; etoposide 100 mg/m2 intravenously on days 1–3; repeated every 21 days); (4) P-GEMOX (pegaspargase 2500 IU/m2 intramuscular injection on days 1, gemcitabine 1000 mg/m2 intravenously on days 1,8, oxaliplatin 130 mg/m2 intravenously on day 1; repeated every 21 days), and asparaginase combined with non-anthracycline drugs. Chemotherapy regimens consisting of three to six cycles were administered based on the clinical characteristics of the patients. In our study, all patients underwent radiotherapy utilizing a 6 MV photon beam. The treatment planning employed either three-dimensional conformal radiotherapy or reverse intensity modulated radiotherapy. For patients with limited stage IE disease, the clinical target volume encompassed the nasal cavity, bilateral frontal ethmoid sinuses, and the ipsilateral maxillary sinus. In cases of extensive stage IE disease, the clinical target volume (CTV) was expanded to include the involved organs and/or tissues. For stage IIE disease, the CTV further incorporated the affected cervical lymph node region. The planning target volume was defined as the CTV with an additional 5 mm margin. The prescribed radiotherapy regimen consisted of 50–56 Gy delivered in 25–28 fractions, with one fraction per day and five fractions per week. Efficacy assessment The clinical efficacy of the treatment was assessed every two to three cycles. Routine examinations were conducted prior to the initiation of each chemotherapy cycle. The criteria for evaluating treatment response were based on the Lugano 2014 standards. These standards incorporate both radiological and metabolic assessments to evaluate treatment response in lymphomas. Specifically, for ENKTL, the treatment response is categorized into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The radiological assessment involves computed tomography (CT) or magnetic resonance imaging (MRI) to mark the six largest target lesions, while the metabolic assessment utilizes positron emission tomography/computed tomography (PET/CT) to evaluate the treatment response in FDG-avid lymphomas. The Deauville 5-point scale is used as the visual evaluation standard for interpreting PET imaging results. For the purpose of this study, outcomes were consolidated into CR and non-CR categories, with the latter encompassing PR, SD, and PD. This bifurcation allowed us to assess the influence of treatment response on patient prognosis. Statistical analysis The optimal cutoff values for ALB concentrations, LDH levels, and LAR were ascertained utilizing receiver operating characteristic (ROC) analysis. OS was determined from diagnosis to the date of death from any cause or the last follow-up visit. Progression-free survival (PFS) was calculated from the date of diagnosis to the initial occurrence of disease progression or relapse, any-cause mortality, or the end of the follow-up period. Kaplan-Meier survival curves were used to analyze the OS and PFS, with the log-rank test utilized to assess and compare survival differences. The Cox proportional hazards model was utilized to calculate the hazard ratio (HR) for OS and to identify significant prognostic factors. Comparisons between categorical variables were made using either the chi-square test or Fisher's exact test, depending on the data distribution. SPSS version 26.0 software (IBM SPSS) and R software (version 4.0.5) were employed for statistical analysis. We considered statistical significance to be present when the two-tailed p-value was less than 0.05. Results Patient characteristics Patient characteristics are listed in Table 1 . The median age of the 484 patients with ENKTL was 41 years (12–79 years), 325 (67.1%) were male and 159 (32.9%) were female. The majority of patients exhibited stage I or II disease, with 453 of 484 patients (93.6%) diagnosed with the nasal-type ENKTL. Table 1 Characteristics of patients Characteristics No. of patients (%, n = 484) Age (years) ≤60 418(86.4) >60 66 (13.6) Gender Male 325(67.1) Female 159(32.9) ECOG PS 0–1 388(80.2) ≥2 96 (19.8) Presence of B symptoms Positive 260 (53.7) Negative 224(46.3) Ann Arbor stage I-II 356(73.6) III-IV 128(26.3) BM invasion Positive 33(6.8) Negative 451(93.2) RLN invasion Positive 200(41.3) Negative 284(58.7) DLN invasion Positive 60(12.4) Negative 424 (87.6) Primary locations Nasal type 453(93.6) Non-nasal type 31(6.4) PINK score 0–1 374(77.3) 2–4 110(22.7) Extranodal sites <2 391(80.8) ≥2 93(19.2) Chemotherapy regimens LVDP 318(65.7%) LVP 44(9.1%) GLIED 61(12.6%) P-GEMOX 26(5.4%) Other asparaginase-based regimens 35(7.2%) LDH concentration (u/L), median(range) 1679(103–3346) ALB concentration (g/L), median(range) 36(21.2–55.9) ECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; PINK, prognostic index of natural killer lymphoma; LDH, lactate dehydrogenase; ALB albumin; LVDP, L-asparaginase, etoposide, dexamethasone and cisplatin; LVP, L-asparaginase, vincristine and prednisone; GLIDE, gemcitabine, L-asparaginase; ifosfamide; dexamethasone and etoposide; P-GEMOX, pegaspargase, gemcitabine and oxaliplatin. ROC analysis was performed to determine the optimal cutoff values of LAR, ALB level, and LDH concentration for predicting OS. The result showed that the corresponding value for LAR was 5.4 (p < 0.001), for ALB level was 40 g/L (p = 0.019), and for LDH concentration was 230 u/L (p 5.4), 178 (36.8%) individuals had high LDH concentrations (>230 u/L) and 207 (42.8%) cases had low ALB levels (< 40 g/L). Stratifying the population according to LAR-associated prognostic score classified 218 (45.0%) patients as low-risk, 147 (30.4%) as intermediate-risk, and 119 (24.6%) as high-risk. Difference of patient characteristics classified by LAR and LAR-associated prognostic score Patient features classified by LAR are presented in Table 2 . A variety of baseline characteristics showed significant differences between the high LAR and low LAR groups, with the exception of age (>60 yeas) and gender (male). The high LAR group tended to have poor ECOG PS, presence of B symptoms, Ann Arbor stage III/IV,, BM invasion, RLN invasion, DLN invasion, non-nasal type disease, two or more extranodal sites, elevated LDH levels, decreased ALB concentrations and positive EBV-DNA load. Furthermore, patients within the high LAR group exhibited a tendency towards higher PINK score, and indicated a more challenging course towards achieving CR following chemotherapy. In this study, 65.7% of the patients received the LVDP regimen, and it was observed that a higher proportion of patients in the low LAR group tended to receive the LVDP regimen, but the difference was not statistically significant. Table 2 Baseline clinical characteristics divided by LAR Characteristics High LAR (n = 194) Low LAR (n = 290) P value Age (years) 0.507 ≤60 170(87.6) 248(85.5) >60 24 (13.4) 42(14.5) Gender 0.590 Female 61 (31.2) 98(33.8) Male 133 (68.6) 192 (66.2) ECOG PS < 0.001 0–1 113(58.2) 275(94.8) ≥2 81 (41.8) 15 (5.2) Presence of B symptoms < 0.001 Positive 144(74.2) 116(40.0) Negative 50 (25.8) 174 (60.0) Ann Arbor stage I-II 97(50.0) 259(89.3) < 0.001 III-IV 97(50.0) 31 (10.7) BM invasion < 0.001 Positive 32(16.5) 1 (0.4) Negative 162(83.5) 289 (99.6) RLN invasion 0.001 Positive 109(56.2) 91(31.2) Negative 85(43.8) 199(68.6) DLN invasion < 0.001 Positive 42 (21.6) 18 (6.2) Negative 152(78.4) 272 (93.8) Primary locations < 0.001 Nasal type 169(87.1) 284(97.9) Non-nasal type 25(13.9) 6(2.1) PINK score < 0.001 0–1 110(56.7) 264(91.0) 2–4 84(43.3) 26(9.0) Extranodal sites < 0.001 <2 118(60.8) 273(94.1) ≥2 76(39.2) 17(5.9) Chemotherapy regimens 0.001 LVDP 106(54.6%) 212(73.1%) LVP 20(10.3%) 24(8.3%) GLIDE 35(18.0%) 26(9.0%) P-GEMOX 14(7.3%) 12(4.1%) Other 19(9.8%) 16(5.5) Response after treatment CR 83(42.8) 218(75.2) non-CR 111(57.2) 72(24.8) ECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; PINK, prognostic index of natural killer lymphoma; LVDP, L-asparaginase, etoposide, dexamethasone and cisplatin; LVP, L-asparaginase, vincristine and prednisone; GLIDE, gemcitabine, L-asparaginase; ifosfamide; dexamethasone and etoposide; P-GEMOX, pegaspargase, gemcitabine and oxaliplatin; CR, complete response On the basis of LAR-associated prognostic score, patients were divided into three risk categories: low- risk (LDH ≤ 230 u/L and ALB ≥ 40 g/L), intermediate-risk (LDH>230 u/L or ALB 230 u/L and ALB < 40 g/L). In addition, among the three risk strata divided according to LAR-associated prognostic score, patients in the lower risk strata were more likely to receive the LVDP regimen, with an increasing tendency towards the lower end of the risk spectrum. Similar to LAR, notable differences in patient characteristics were found in different risk groups, with the exception of age and gender (Table 3 ). Table 3 Baseline clinical characteristics divided by LAR-associated prognostic score Characteristics Low risk (n = 218) Intermediate risk (n = 147) High risk (n = 119) P value Age (years) 0.134 ≤60 189(86.7) 121(82.3) 108(90.8) >60 29 (13.3) 26(17.7) 11(9.2) Gender 0.915 Female 73 (33.5) 51(34.7) 35(29.4) Male 145 (66.5) 96 (65.3) 84(70.6) ECOG PS < 0.001 0–1 204(93.6) 126(85.7) 58(48.8) ≥2 14 (6.4) 21 (14.3) 61(51.2) Presence of B symptoms < 0.001 Positive 74(33.9) 85(57.8) 102(85.7) Negative 144 (66.1) 62 (42.8) 17(14.3) Ann Arbor stage I-II 194(89.0) 112(76.2) 50(42.0) < 0.001 III-IV 24(11.0) 35 (23.8) 69(58.0) BM invasion < 0.001 Positive 1(0.5) 6(4.1) 27(22.7) Negative 217(99.5) 141 (95.9) 92(77.3) RLN invasion < 0.001 Positive 65(29.9) 66(44.9) 70(58.8) Negative 153(70.1) 81(55.1) 49(41.2) DLN invasion < 0.001 Positive 13 (6.0) 20 (13.6) 28(23.5) Negative 205(94.0) 127(86.4) 91(76.5) Primary locations < 0.001 Nasal type 213(97.7) 136(92.5) 98(82.4) Non-nasal type 5(2.3) 11(7.5) 21(17.6) PINK score < 0.001 0–1 199(91.3) 117(79.6) 58(48.7) 2–4 17(8.7) 30(20.4) 61(51.3) Extranodal sites < 0.001 <2 205(94.0) 125(85.0) 61(51.3) ≥2 13(6.0) 22(15.0) 58(48.7) Chemotherapy regimens 0.001 LVDP 157(72.1%) 98(66.7%) 63(52.9%) LVP 16(7.3%) 18(12.2%) 10(8.4%) GLIDE 22(10.1%) 10(6.8%) 29(24.4%) P-GEMOX 9(4.1%) 13(8.9%) 4(3.4%) Other 14(6.4%) 8(5.4%) 13(10.9%) Response after treatment < 0.001 CR 172(78.9) 86(58.5) 43(36.2) non-CR 46(21.1) 61(41.5) 76(63.8) ECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; PINK, prognostic index of natural killer lymphoma; LVDP, L-asparaginase, etoposide, dexamethasone and cisplatin; LVP, L-asparaginase, vincristine and prednisone; GLIDE, gemcitabine, L-asparaginase; ifosfamide; dexamethasone and etoposide; P-GEMOX, pegaspargase, gemcitabine and oxaliplatin; CR, complete response Survival analysis and prognosis factors Following a median follow-up period of 70 months, spanning from 1 to 144 months, 47.7% (231 of 484) of the patients experienced disease progression or relapse, and 41.3% (200 of 484) of the patients had died. The estimated 5-year OS and PFS rates for these 484 patients were 58.7% and 52.0%, respectively (Fig. 2 ). The univariate Cox regression analysis identified the following parameters with significant correlations to OS: ECOG PS (≥ 2), presence of B symptoms, Ann Arbor stage III/IV, non-nasal disease classification, BM invasion, RLN invasion, DLN invasion, non-CR response, elevated LDH concentrations (>230 u/L), decreased ALB levels (5.4), and the LAR-associated prognostic score (Table 4 ). Separate multivariate analyses were conducted incorporating LDH and ALB levels, the LAR, and the LAR-associated prognostic score. The findings indicated that advanced poor ECOG PS, RLN invasion and non-CR response after chemotherapy were adverse prognostic indicators. Of particular significance, LDH>230 u/L (p = 0.003), ALB 5.4 (p < 0.001), and the LAR-associated prognostic score (p < 0.001) were substantially correlated with patient outcomes in ENKTL (Tables 5 , 6 , 7 ). The concordance statistic (C-index) for survival prediction was 0.70 (95% confidence interval (CI), 0.66–0.73) using LDH and ALB classification, 0.67 (95% CI, 0.63–0.70) using the LAR classification, and 0.70 (95% CI, 0.66–0.73) using the LAR-associated prognostic score classification, respectively. Table 4 Univariate analysis of overall survival Characteristics Relative risk (95% CI), p value Age (>60 years) 0.780 (0.505–1.205),0.259 Gender (male) 1.542 (1.124–2.116),0.006 ECOG PS (≥ 2) 3.083 (2.263-4.200),<0.001 Presence of B symptoms 1.838 (1.377–2.455),<0.001 Ann Arbor stage (III-IV) 2.972 (2.235–3.952),<0.001 BM invasion 3.387 (2.202–5.208),<0.001 RLN invasion 2.068 (1.564–2.735),<0.001 DLN invasion 1.924 (1.335–2.773),<0.001 Primary locations (non-nasal type) 2.392 (1.521–3.761),<0.001 Extranodal sites ≥ 2 3.080 (2.276–4.168),<0.001 Response after treatment (non-CR) 1.688 (1.533–1.858),<0.001 PINK score (≥ 2) 2.960 (2.212–3.960),<0.001 ALB(<40 g/L) 2.943 (2.221–3.917),230 u/L) 2.880 (2.176–3.813),<0.001 LAR 3.253 (2.448–4.332),<0.001 LAR-associated prognostic score 2.256 (1.895–2.687), <0.001 ECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; CR, complete remission; PINK, prognostic model for natural killer lymphoma; ALB, albumin; LDH, lactate dehydrogenase;LAR, lactate dehydrogenase to albumin ratio; CI, confidence interval Table 5 Multivariate analysis of overall survival according to LDH and ALB Characteristics Relative risk (95% CI), p value Age (>60 years) Gender (male) ECOG PS (≥ 2) 1.504 (1.019–2.221), 0.04 Presence of B symptoms Ann Arbor stage (III-IV) BM invasion RLN invasion 1.408 (1.047–1.8093), 0.024 DLN invasion Primary locations (non-nasal type) Extranodal sites ≥ 2 Response after treatment (non-CR) 1.592(1.422–1.783), <0.001 ALB(230 u/L) 1.660 (1.185–2.327), 0.003 ECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; CR, complete remission; ALB, albumin; LDH, lactate dehydrogenase; CI, confidence interval Table 6 Multivariate analysis of overall survival according to LAR Characteristics Relative risk (95% CI), p value Age (>60 years) Gender (male) ECOG PS (≥ 2) Presence of B symptoms Ann Arbor stage (III-IV) BM invasion RLN invasion 1.406 (1.046–1.890), 0.024 DLN invasion Primary locations (non-nasal type) Extranodal sites ≥ 2 Response after treatment (non-CR) 1.659 (1.484–1.856), 5.4) 2.182 (1.548–3.075), <0.001 ECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; CR, complete remission; LAR, lactate dehydrogenase to albumin ratio; CI, confidence interval Table 7 Multivariate analysis of overall survival according to LAR-associated prognostic score Characteristics Relative risk (95% CI), p value Age (>60 years) Gender (male) ECOG PS (≥ 2) 1.496 (1.019–2.197), 0.04 Presence of B symptoms Ann Arbor stage (III-IV) BM invasion RLN invasion 1.406 (1.046–1.889), 0.024 DLN invasion Primary locations (non-nasal type) Extranodal sites ≥ 2 Response after treatment (non-CR) 1.595 (1.426–1.783), 5.4) 1.696 (1.372–2.096), <0.001 ECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; CR, complete remission; LAR, lactate dehydrogenase to albumin ratio; CI, confidence interval Data on EBV-DNA were accessible for 345 individuals within this study. Our results revealed that PINK-E scores and EBV-DNA load were associated with prognosis in ENKTL patients with available EBV-DNA data (Supplementary table 2 ). Subsequently, we conducted additional analyses to assess the prognostic significance of LDH and ALB levels, the LAR, and the LAR-associated prognostic score within this group. Separate multivariate analyses were performed with LDH and ALB, the LAR, and the LAR-associated prognostic score. The findings indicated that the incorporation of EBV-DNA data in this patient subset substantiated the association of LDH and ALB levels, the LAR, and the LAR-associated prognostic score with patient outcomes. The relative risk associated with these factors remained consistent when compared to the entire cohort (Supplementary tables 3,4,5). The prognostic significance of LAR and LAR-associated prognostic score Patients possessing low LAR demonstrated significantly better prognosis compared those with high LAR. The 5-year OS rates for patients in low LAR and high LAR groups were 69.6% and 36.3%, respectively (p < 0.0001) (Fig. 3 A). Improved PFS was also found in patients with low LAR. The 5-year PFS rates for patients in low LAR and high LAR groups were 66.3% and 30.4%, respectively (p < 0.0001) (Fig. 3 B). According to LAR-associated prognostic score, patients were classified into low-risk, intermediate-risk, and high-risk groups. Significant differences on 5-year OS (low-risk versus (vs.) intermediate-risk, 77.4% vs. 55.0%, p < 0.0001; low-risk vs. high-risk, 77.4% vs. 29.3%, p < 0.0001; intermediate-risk vs. high-risk, 55.0% vs. 29.3%, p < 0.0001; Fig. 4 A) and PFS (low-risk vs. intermediate-risk, 69.8% vs. 46.0%, p < 0.0001; low-risk vs. high-risk, 69.8% vs. 26.8%, p < 0.001; intermediate-risk vs. high-risk, 46.0% vs. 26.8%, p < 0.0001; Fig. 4 B) also have been identified. For the 345 patients with available EBV-DNA data, the 5-year OS rates for patients in low LAR and high LAR groups were 73.7% and 58.5%, respectively (p < 0.0001; supplementary Fig. 1A), and the 5-year PFS patients in low LAR and high LAR groups were 65.8% and 33.7%, respectively (p < 0.0001, supplementary Fig. 1B). According to LAR-associated prognostic score, the 345 patients were also classified into low-risk, intermediate-risk, and high-risk groups. Significant differences on 5-year OS (low-risk vs. intermediate-risk, 79.1% vs. 57.5%, p < 0.0001; low-risk vs. high-risk, 79.1% vs. 30.7%, p < 0.0001; intermediate-risk vs. high-risk, 57.5% vs. 30.7%, p < 0.0001; supplementary Fig. 2A) and PFS (low-risk vs. intermediate-risk, 70.9% vs. 48.7%, p < 0.0001; low-risk vs. high-risk, 70.9% vs. 27.0%, p < 0.0001; intermediate-risk vs. high-risk, 48.7% vs. 27.0%, p < 0.0001; supplementary Fig. 2B) also have been identified. Utilizing the PINK and PINK-E models, patients were categorized into three distinct risk groups, which exhibited significant differences in survival outcomes. Despite evaluating the PINK model, no significant distinction in survival outcomes was observed between the low-risk and intermediate-risk groups (p = 0.792). Within this model, the 5-year OS rates were recorded at 66.1% for the low-risk group, 63.3% for intermediate-risk group, and 32.8% for the high-risk group. A similar pattern emerged when applying the PINK-E model, where no discernible difference was found between the low-risk and intermediate-risk groups (p = 0.405). The 5-year OS rates for the PINK-E model were 69.6% for the low-risk group, 59.9% for the intermediate-risk group, and 31.6% for the high-risk group. We sought to further stratify the patients by separately integrating the LAR and LAR-associated prognostic score into the PINK and PINK-E models. In subgroup analyses within the low-risk and intermediate-risk as defined by the PINK system, the prognostic significance of the LAR and the LAR-associated prognostic score was demonstrated, revealing additional prognostic insights. The 5-year OS rates were 74.8% for the low LAR group and 54.6% for the high LAR group (p < 0.0001, Fig. 5 A). Furthermore, when stratified by the LAR-associated prognostic score into low-, intermediate-, and high-risk groups, the respective 5-year OS rates were 85.7%, 60.8%, and 41.3%, respectively (p < 0.0001, Fig. 5 B). Similarly, the LAR and LAR-associated prognostic score demonstrated enhanced capability in identifying survival disparities among patients categorized into the low-risk and intermediate-risk group according to the PINK-E index. The 5-year OS rates were 73.7% for the low LAR group and 39.7% for the high LAR group (p < 0.0001, Fig. 6 A). Additionally, when classified by the LAR-associated prognostic score into low-, intermediate-, and high-risk groups, the respective 5-year OS rates were 79.1%, 57.5%, and 30.7%, respectively (p < 0.0001, Fig. 6 B). Discussion Previous studies have established that LDH and ALB levels in patients with DLBCL hold substantial prognostic significance and can serve as valuable factors in clinical assessments of patient outcomes [ 20 – 23 ] . Furthermore, the LAR has emerged as a potential prognostic indicator in disease evaluation, albeit with scant data linking it specifically to DLBCL [ 19 ] . Our study marks the inaugural investigation into the correlation between the LAR and prognosis in ENKTL patients receiving asparaginase-based chemotherapy. Research indicates that ALB concentrations impact bodily metabolism, nutritional status, and the transport of substrates [ 24 ] . Additionally, the state of nutrition and inflammation can lead to a decrease in ALB synthesis, positioning ALB as an indicator of overall systemic nutrition and a straightforward measure of inflammatory response [ 25 ] . It is notable that ALB also plays a role in extending drug half-life and mitigating toxicity [ 26 ] . Due to diverse mechanisms related to the tumor itself, the host's reaction to the tumor, and the effects of anticancer treatments, malnutrition can lead to substantial complications for patients with malignancies [ 27 ] . Persistent hypoproteinemia serves as a straightforward and potent indicator of poor prognosis in patients with DLBCL, and post-treatment follow-up should particularly attend to patients presenting with hypoalbuminemia [ 28 ] . Integrating early alterations in ALB levels with established biomarkers has demonstrated potential to enhance the predictive accuracy of prognostic outcomes for patients with non-small cell lung cancer undergoing monotherapy with immune checkpoint inhibitors [ 29 ] . The swift division of cancer cells is accompanied by a heightened rate of glucose consumption and irregular functioning of LDH, which is crucial for the metabolic process that transforms glucose into lactate [ 30 ] . Increased LDH levels predict adverse prognosis for hematologic malignancies, indicating a substantial tumor burden and aggressive disease course. Elevated serum LDH levels significantly influence the prognosis for achieving CR in patients with lymphoma. LDH is also recognized as one of the diagnostic criteria for various lymphoma prognostic systems. The LAR, a composite of LDH and ALB levels, offers a comprehensive assessment of the body's inflammatory response, nutritional status, and tumor burden, providing a holistic view of a patient's condition. Previous studies have demonstrated the association between LAR and prognosis in various malignancies [ 16 – 19 ] , establishing it as an independent poor prognostic factor. However, the prognostic significance of LAR in ENKTL has not yet been reported. This is the first study to evaluate the association between the LAR and prognosis in ENKTL patients receiving asparaginase-based therapy regimens. As there were no specific criteria for the optimal cutoff values of ALB and LDH, ROC analyses were conducted to determine these values for LDH, ALB, and LAR, which were found to be 230 u/L, 40 g/L, and 5.4, respectively (p < 0.001). Multivariate analysis revealed that ALB 230 u/L and LAR>5.4, each independently correlated with poor prognostic outcomes for OS (p < 0.001). Our study revealed a significant difference in clinical outcomes between the high and low LAR groups. Specifically, patients in the high LAR group had worse 5-year OS and PFS, as shown in Fig. 3 A and 3 B. Furthermore, our study identified significant differences in clinical manifestations and outcomes between patients with high LAR and those with low LAR. The high LAR group was more likely to exhibit unfavorable characteristics, such as poor ECOG PS, advanced disease stage, B symptoms, non-CR after chemotherapy etc. We proceeded to examine the significance of the LAR-associated prognostic score in ENKTL. Utilizing this scoring system, patients were categorized into three risk groups, determined by their serum LDH and ALB levels. A notable variation in prognostic outcomes were detected among patients classified into various risk groups, with higher scores correlating to adverse outcomes (Fig. 4 A and 4 B). Similar to LAR, patients with higher scores tended to have more unfavorable characteristics. EBV-DNA serves as a significant biomarker for tumor burden, given that ENKTL tumor cells are persistently infected with the EBV. The diagnosis of ENKTL is confirmed by the presence of a positive viral titer through in situ hybridization. Additionally, the presence of EBV-DNA in peripheral blood is intimately linked to the survival rates and therapeutic outcomes for ENKTL patients [ 31 , 32 ] . The definitive threshold for the EBV-DNA titer remains unclear, with virtually all research considering a positive EBV-DNA status if any measurable concentration is present in the blood at diagnosis [1,31–33 ] . In this study, 484 patients with ENKTL were included, among which 345 cases had available EBV data. We further analyzed the prognostic value of LAR in the population with available EBV data. Our findings showed a notable disparity in clinical outcomes between patients with high and low LAR values. Notably, those in the high LAR group exhibited poorer 5-year OS and PFS rates, as illustrated in Supplementary Fig. 1A and 1B. We advanced our investigation to assess the relevance of the LAR-associated prognostic score among ENKTL patients with accessible EBV-DNA data. With the application of this scoring system, participants were divided into three distinct risk groups. Significant differences in prognostic outcomes were observed among these groups, with higher scores indicating a correlation with unfavorable outcomes, as depicted in Supplementary Figs. 2A and 2B. The PINK and PINK-E models are referred as novel prognostic scoring systems for ENKTL [ 1 ] . In both the PINK and PINK-E classification systems, the outcomes between the low-risk and intermediate-risk groups did not exhibit significant differences. When the LAR and LAR-associated prognostic score were applied separately to evaluate the low-risk and intermediate-risk groups defined by the PINK system, substantial variations in survival rates were noted. These differences were evident between the groups with low versus high LAR values, as well as across the categorized low-, intermediate-, and high-risk groups based on the LAR-associated prognostic score. Applying the LAR and LAR-associated prognostic score to assess the low-risk and intermediate-risk groups in the PINK-E system yielded comparable findings. There were some limitations in this study. Firstly, this study represents a single-center analysis, and its findings necessitate further validation across diverse populations to ensure broader applicability and reliability. Secondly, the retrospective design of this study could have potentially led to the introduction of selection bias and information bias. Therefore, future prospective studies are needed to validate our results. Conclusion The present study is the first to demonstrate the prognostic value of the LAR and LAR-associated prognostic score in patients with ENKTCL. The findings indicate that both LAR and LAR-associated prognostic score are correlated with the outcomes of patient with ENKTCL, and they notably enhance the precision of prognostic assessment, thereby improving the efficacy of clinical decision-making. Declarations Data availability statement The novel findings of this study are detailed within the article and its supplementary materials. For additional inquiries or clarifications, readers should contact the corresponding author. Funding The authors declare that no financial support was received. Ethics approval and consent to participate All procedures performed in this study were approved by the institutional review boards (IRB) at West China Fourth Hospital, Sichuan University and in accordance with the ethical standards of the institutions and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Due to the retrospective nature of this study, informed consent was not required by the IRB at West China Fourth Hospital, Sichuan University. Conflict of interest The authors state that no commercial or financial interests influenced the research, eliminating any potential conflicts of interest. References Kim SJ, Yoon DH, Jaccard A, et al. A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis. Lancet Oncol. 2016;17:389-400. Tse E, Kwong YL. How I treat NK/T‐cell lymphomas. Blood. 2013;121(25):4997-5005. Yamaguchi M, Kita K, Miwa H, et al. Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells. Cancer. 1995;76(11):2351-2356. NCCN Guidelines T-Cell Lymphomas Version 1. 2024. Bi XW, Xia Y, Zhang WW, et al. Radiotherapy and PGEMOX/GELOX regimen improved prognosis in elderly patients with early-stage extranodal NK/T-cell lymphoma. Ann Hematol. 2015;94(9):1525-1533. Cheung MM, Chan JK, Lau WH, et al. Early stage nasal NK/T-cell lymphoma: clinical outcome, prognostic factors, and the effect of treatment modality. Int J Radiat Oncol Biol Phys. 2002;54(1):182-190. Hong H, Li Y, Lim ST, et al. A proposal for a new staging system for extranodal natural killer T-cell lymphoma: a multicenter study from China and Asia lymphoma study group. Leukemia. 2020;34(8):2243-2248. International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993;329(14):987-994. Lee J, Suh C, Park YH, et al. Extranodal natural killer T-cell lymphoma, nasal-type: a prognostic model from a retrospective multicenter study. J Clin Oncol. 2006;24(4):612-618. Kim SJ, Yoon DH, Jaccard A, et al. A prognostic index for natural killer cell lymphoma after nonanthracycline-based treatment: a multicenter, retrospective analysis. Lancet Oncol. 2016;17(3):389-400. Chen SY, Yang Y, Qi SN, et al. Validation of nomogram-revised risk index and comparison with other models for extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: indication for prognostication and clinical decision-making. Leukemia. 2021;35(1):130-142. Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer. 2002;2(11):862-871. Gordon JN, Green SR, Goggin PM. Cancer cachexia. QJM.2005; 98(11):779-788. Infusino I, Panteghini M. Serum albumin: accuracy and clinical use. Clin Chim Acta. 2013;419:15-18. Ding J, Karp JE, Emadi A. 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Association between serum albumin levels and survival in elderly patients with diffuse large B-cell lymphoma: a single-center retrospective study. Transl Cancer Res. 2023;12(6):1577-1587. Wei X, Zheng J, Zhang Z, et al. Consecutive hypoalbuminemia predicts inferior outcome in patients with diffuse large B-cell lymphoma. Front Oncol. 2021;10:610681. Bakirtas M, Basci S, Candır BA, et al. Prognostic value of neutrophil/lymphocyte ratio, lymphocyte/monocyte ratio, lactate dehydrogenase, and mean platelet volume in the diagnosis of patients with diffuse large B-cell lymphoma. Egypt J Haematology. 2022;47(4):233-238. Tyagi A, Abrari A, Khurana A, et al. Immunohistochemical subtyping of diffuse large Bcell lymphoma into germinal center B-cell and activated B-cell subtype, along with correlation of the subtypes with extranodal involvement, serum lactate dehydrogenase, and positron emission tomography scan-based response assessment to chemotherapy. J Cancer Res Ther. 2022;18(4):1129-1136. Tessari P. Protein metabolism in liver cirrhosis: from albumin to muscle myofibrils. Curr Opin Clin Nutr Metab Care. 2003;6(1):79-85. Fanali G, di Masi A, Trezza V, et al. Human serum albumin: from bench to bedside. Mol Asp Med. 2012;33(3):209-290. Ghuman J, Zunszain PA, Petitpas I, et al. Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol. 2005;353(1):38-52. von Meyenfeldt M. Cancer-associated malnutrition: an introduction. Eur J Oncol Nurs. 2005;9(Suppl 2):S35-S38. Kaneko H, Shimura K, Yoshida M, et al. Serum albumin levels strongly predict survival outcome of elderly patients with diffuse large B-cell lymphoma treated with rituximab-combined chemotherapy. Int J Hematol Oncol Stem Cell Res. 2022;16(1):1-8. Guo Y, Wei L, Patel SH, et al. Serum albumin: early prognostic marker of benefit for immune checkpoint inhibitor monotherapy but not chemoimmunotherapy. Clin Lung Cancer. 2022;23(4):345-355. de la Cruz-López KG, Castro-Muñoz LJ, ReyesHernández DO, et al. Lactate in the regulation of tumor microenvironment and therapeutic approaches. Front Oncol. 2019;9:1143. Kim HS, Kim KH, Kim KH et al. Whole blood Epstein–Barr virus DNA load as a diagnostic and prognostic surrogate: extranodal natural killer/T-cell lymphoma. Leuk. Lymphoma. 2009; 50, 757-763. Ito Y, Kimura H, Maeda Y et al. Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type. Clin. Cancer Res. 2012;18, 4183-4190. Chan KCA, Zhang J, Chan ATC et al. Molecular characterization of circulating EBV DNA in the plasma of nasopharyngeal carcinoma and lymphoma patients. Cancer Res.2003; 63(9), 2028–2032. Additional Declarations No competing interests reported. Supplementary Files SFigure1.tif Supplementary figure 1: Survivals in patients with available EBV-DNA data stratified by LAR: (A) overall survival and (B) progression-free survival. SFigure2.tif Supplementary figure 2: Survivals in patients with available EBV-DNA data stratified by LAR-associated prognostic score: (A) overall survival and (B) progression-free survival. supplementarytable1.docx supplementarytable2.docx supplementarytable3.docx supplementarytable4.docx supplementarytable5.docx Cite Share Download PDF Status: Published Journal Publication published 15 Jul, 2025 Read the published version in BMC Cancer → Version 1 posted Editorial decision: Revision requested 02 May, 2025 Reviews received at journal 22 Apr, 2025 Reviewers agreed at journal 09 Apr, 2025 Reviews received at journal 04 Apr, 2025 Reviewers agreed at journal 04 Apr, 2025 Reviewers invited by journal 04 Apr, 2025 Submission checks completed at journal 04 Apr, 2025 First submitted to journal 04 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5503269","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":438673581,"identity":"820e39ca-ec4f-437b-a106-0c358757587c","order_by":0,"name":"Na 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1","display":"","copyAsset":false,"role":"figure","size":431986,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operating curve for determining the optimal cut-off value for survival for (A) LAR, (B) ALB, and (C) LDH.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5503269/v1/b021c3031ea4b579e37e2619.png"},{"id":80063126,"identity":"e0ebcf2a-014e-4a60-81ec-651391e94f30","added_by":"auto","created_at":"2025-04-07 12:42:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":104731,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival curves of enrolled patients: (A) overall survival and (B) progression-free 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12:42:29","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":5881060,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary figure 1: Survivals in patients with available EBV-DNA data stratified by LAR: (A) overall survival and (B) progression-free survival.\u003c/p\u003e","description":"","filename":"SFigure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-5503269/v1/874e935418e53abb325a460d.tif"},{"id":80064002,"identity":"df549d7d-c01a-4fb3-92e8-4102af18c0b1","added_by":"auto","created_at":"2025-04-07 12:50:31","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":5989020,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary figure 2: Survivals in patients with available EBV-DNA data stratified by LAR-associated prognostic score: (A) overall survival and (B) progression-free 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12:50:29","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":14806,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarytable4.docx","url":"https://assets-eu.researchsquare.com/files/rs-5503269/v1/2f25e739767176edbab40e31.docx"},{"id":80064001,"identity":"a96c8231-1909-49b9-b962-4b3a2b33446f","added_by":"auto","created_at":"2025-04-07 12:50:30","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":14814,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarytable5.docx","url":"https://assets-eu.researchsquare.com/files/rs-5503269/v1/58f181a33c5d9d1534c56459.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The prognostic value of lactate dehydrogenase/albumin ratio in extranodal natural killer/T cell lymphoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eExtranodal natural killer/T-cell lymphoma (ENKTL) represents a heterogeneous disease with a predominant manifestation in the nasal cavity and nasopharynx, exhibiting a strong association with Epstein-Barr virus (EBV) infection \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Approximately 10\u0026ndash;20% of these lymphomas arise in locations outside the nasal cavity, including the skin, testes, gastrointestinal tract, muscle, and salivary glands \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. ENKTL is more prevalent in Asia and, to a lesser degree, in Latin America, while it is considered rare in European and North American. ENKTL cells exhibit elevated levels of P-glycoprotein, which confers resistance to anthracycline-based therapies \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Given the enhanced survival outcomes observed in patients with ENKTL, treatment protocols incorporating asparaginase are currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. However, despite the advances, a significant number of patients still relapse and become refractory, leading to an unsatisfactory prognosis \u003csup\u003e[\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIdentifying and confirming the clinical risk factors in patients with ENKTL can enhance the accuracy of prognosis by enabling more precise stratification, and in turn, offer valuable insights to guide clinical treatment decisions. The International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) models were developed in anthracycline-based era. However, utilizing these models, the survival for patients undergoing asparaginase-based therapies were not able to be precisely categorized \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. The prognostic index for natural killer lymphoma (PINK) and PINK with Epstein-Barr virus (PINK-E) models have demonstrated validity in ENKTL, but they have not yet effectively identified risk categories for patients with early-stage disease \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Despite the nomogram-revised risk index (NRI) showing a higher predictive accuracy for overall survival (OS) when compared to the well-established IPI, KPI, PINK, and PINK-E models, it is crucial to recognize that these indices do not account for patients' comorbidities \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMalnutrition is prevalent among patients with malignancy, affecting approximately 80% of those in the advanced stages of their disease \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Despite a limited comprehension of the precise mechanisms behind nutritional alterations in malignancy, it is recognized that catabolic substances released by tumor cells, in conjunction with the host's inflammatory reactions, can lead to increased energy expenditure. This can cause a reduction in body weight and may culminate in malnutrition \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. As the predominant plasma protein, serum albumin (ALB) offers a readily measurable indicator. Extensively utilized in clinical settings, it serves as a vital component in the prognostic evaluation of a variety of medical conditions \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Tumor cells exhibit increased metabolic activity, characterized by elevated glucose consumption and lactate output. Lactate dehydrogenase (LDH) is a marker that is conveniently and routinely measured in patients with malignancy, providing insights into the tumor load. Increased levels of LDH, serving as an adverse prognostic indicator, facilitate the suppression and evasion of the immune system by tumor cells through the modification of the tumor microenvironment \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eLevels of ALB and LDH offer crucial insights into a patient's immune function, inflammatory activity, and tumor burden, establishing themselves as significant prognostic markers across various malignancies. Although previous studies have highlighted the prognostic relevance of the lactate dehydrogenase/albumin ratio (LAR) in colon cancer \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e, gastric cancer \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e, breast cancer \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e, and diffuse large B-cell lymphoma (DLBCL) \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e, its predictive value in ENKTL has not been reported. Therefore, we conducted a study to explore the predictive value of the LAR and LAR-associated prognostic score toward the prognosis of ENKTL patients receiving asparaginase-containing regimens.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003e Between January 2009 and January 2020, a retrospective review was conducted on 484 patients with ENKTL, extracted from medical records. The inclusion criteria were: (1) a pathological diagnosis of ENKTL without a history of prior antitumor treatments; (2) absence of any previous or concurrent malignancies; (3) chemotherapy regimens including L-asparaginase or pegaspargase, and (4) availability of comprehensive clinical, laboratory data, and follow-up details.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eClinical data were collected as follows: age, gender, Eastern Cooperative Oncology Group (ECOG) performance status (PS), primary site of the lesion, regional lymph node invasion (RLN), distant lymph node invasion (DLN), extranodal invasion, bone marrow (BM) invasion, B symptoms, and Ann Arbor stage. Laboratory parameters including ALB levels, LDH concentrations, and EBV-DNA titer. A measurable level of EBV-DNA was considered positive due to the lack of a universally agreed-upon optimal cutoff value for EBV titer in predicting prognosis. Previous models including PINK (age, stage, non-nasal type, DLN) and PINK-E (age, stage, non-nasal type, DLN, and EBV-DNA status) were also used to enforce survival analysis. Pretreatment LAR was calculated as lactate dehydrogenase/albumin ratio. We proceeded to combine the categorized levels of LDH and ALB to generate the LAR-associated prognostic score, categorizing patients into three risk groups: low-risk (normal LDH and ALB levels), intermediate-risk (high LDH or low ALB levels), and high-risk (high LDH and low ALB levels) (Supplementary tabl\u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003ee1\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eTreatment\u003c/h3\u003e\n\u003cp\u003eA total of 346 patients (71.5%) received chemoradiotherapy and 138 cases (28.5%) underwent chemotherapy. The chemotherapy regimens were formulated with either L-asparaginase or pegaspargase as their foundation and primarily included the following combinations: (1) LVDP (L-asparaginase 6000 IU/m2 intravenously on days 1\u0026ndash;5, etoposide 80 mg/m2 intravenously on days 1\u0026ndash;3, dexamethasone 40 mg/day intravenously on days 1\u0026ndash;4, cisplatin 25 mg/m2 intravenously on days 1\u0026ndash;3; repeated every 21 days); (2) LVP (L-asparaginase 5500 IU/m2 intravenously on days 1\u0026ndash;5, vincristine 1.4 mg/m2 given intravenously on day 1, prednisone 100 mg orally on days 1\u0026ndash;5; repeated every 21 days); (3) GLIED (gemcitabine 1000 mg/m2 intravenously on days 1, 8, L-asparaginase 6000 IU/m2 intravenously on days 4, 6, 8, 10, 12; ifosfamide 1000 mg/m2 intravenously on days 1\u0026ndash;3; dexamethasone 20 mg intravenously on days 1\u0026ndash;4; etoposide 100 mg/m2 intravenously on days 1\u0026ndash;3; repeated every 21 days); (4) P-GEMOX (pegaspargase 2500 IU/m2 intramuscular injection on days 1, gemcitabine 1000 mg/m2 intravenously on days 1,8, oxaliplatin 130 mg/m2 intravenously on day 1; repeated every 21 days), and asparaginase combined with non-anthracycline drugs. Chemotherapy regimens consisting of three to six cycles were administered based on the clinical characteristics of the patients.\u003c/p\u003e \u003cp\u003eIn our study, all patients underwent radiotherapy utilizing a 6 MV photon beam. The treatment planning employed either three-dimensional conformal radiotherapy or reverse intensity modulated radiotherapy. For patients with limited stage IE disease, the clinical target volume encompassed the nasal cavity, bilateral frontal ethmoid sinuses, and the ipsilateral maxillary sinus. In cases of extensive stage IE disease, the clinical target volume (CTV) was expanded to include the involved organs and/or tissues. For stage IIE disease, the CTV further incorporated the affected cervical lymph node region. The planning target volume was defined as the CTV with an additional 5 mm margin. The prescribed radiotherapy regimen consisted of 50\u0026ndash;56 Gy delivered in 25\u0026ndash;28 fractions, with one fraction per day and five fractions per week.\u003c/p\u003e\n\u003ch3\u003eEfficacy assessment\u003c/h3\u003e\n\u003cp\u003eThe clinical efficacy of the treatment was assessed every two to three cycles. Routine examinations were conducted prior to the initiation of each chemotherapy cycle. The criteria for evaluating treatment response were based on the Lugano 2014 standards. These standards incorporate both radiological and metabolic assessments to evaluate treatment response in lymphomas. Specifically, for ENKTL, the treatment response is categorized into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The radiological assessment involves computed tomography (CT) or magnetic resonance imaging (MRI) to mark the six largest target lesions, while the metabolic assessment utilizes positron emission tomography/computed tomography (PET/CT) to evaluate the treatment response in FDG-avid lymphomas. The Deauville 5-point scale is used as the visual evaluation standard for interpreting PET imaging results. For the purpose of this study, outcomes were consolidated into CR and non-CR categories, with the latter encompassing PR, SD, and PD. This bifurcation allowed us to assess the influence of treatment response on patient prognosis.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe optimal cutoff values for ALB concentrations, LDH levels, and LAR were ascertained utilizing receiver operating characteristic (ROC) analysis. OS was determined from diagnosis to the date of death from any cause or the last follow-up visit. Progression-free survival (PFS) was calculated from the date of diagnosis to the initial occurrence of disease progression or relapse, any-cause mortality, or the end of the follow-up period. Kaplan-Meier survival curves were used to analyze the OS and PFS, with the log-rank test utilized to assess and compare survival differences. The Cox proportional hazards model was utilized to calculate the hazard ratio (HR) for OS and to identify significant prognostic factors. Comparisons between categorical variables were made using either the chi-square test or Fisher's exact test, depending on the data distribution. SPSS version 26.0 software (IBM SPSS) and R software (version 4.0.5) were employed for statistical analysis. We considered statistical significance to be present when the two-tailed p-value was less than 0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003ePatient characteristics are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age of the 484 patients with ENKTL was 41 years (12\u0026ndash;79 years), 325 (67.1%) were male and 159 (32.9%) were female. The majority of patients exhibited stage I or II disease, with 453 of 484 patients (93.6%) diagnosed with the nasal-type ENKTL.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. of patients (%, n\u0026thinsp;=\u0026thinsp;484)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e418(86.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (13.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e325(67.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e159(32.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG PS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e388(80.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96 (19.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of B symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e260 (53.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e224(46.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnn Arbor stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e356(73.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128(26.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBM invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33(6.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e451(93.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200(41.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e284(58.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60(12.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e424 (87.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary locations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasal type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e453(93.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-nasal type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31(6.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePINK score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e374(77.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e110(22.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtranodal sites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e391(80.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93(19.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy regimens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVDP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e318(65.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(9.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLIED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61(12.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP-GEMOX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26(5.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther asparaginase-based regimens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35(7.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH concentration (u/L), median(range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1679(103\u0026ndash;3346)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALB concentration (g/L), median(range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36(21.2\u0026ndash;55.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; PINK, prognostic index of natural killer lymphoma; LDH, lactate dehydrogenase; ALB albumin; LVDP, L-asparaginase, etoposide, dexamethasone and cisplatin; LVP, L-asparaginase, vincristine and prednisone; GLIDE, gemcitabine, L-asparaginase; ifosfamide; dexamethasone and etoposide; P-GEMOX, pegaspargase, gemcitabine and oxaliplatin.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eROC analysis was performed to determine the optimal cutoff values of LAR, ALB level, and LDH concentration for predicting OS. The result showed that the corresponding value for LAR was 5.4 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), for ALB level was 40 g/L (p\u0026thinsp;=\u0026thinsp;0.019), and for LDH concentration was 230 u/L (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). As is demonstrated, 194 (40.1%) patients had high LAR (\u0026gt;5.4), 178 (36.8%) individuals had high LDH concentrations (\u0026gt;230 u/L) and 207 (42.8%) cases had low ALB levels (\u0026lt;\u0026thinsp;40 g/L). Stratifying the population according to LAR-associated prognostic score classified 218 (45.0%) patients as low-risk, 147 (30.4%) as intermediate-risk, and 119 (24.6%) as high-risk.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDifference of patient characteristics classified by LAR and LAR-associated prognostic score\u003c/h3\u003e\n\u003cp\u003ePatient features classified by LAR are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. A variety of baseline characteristics showed significant differences between the high LAR and low LAR groups, with the exception of age (\u0026gt;60 yeas) and gender (male). The high LAR group tended to have poor ECOG PS, presence of B symptoms, Ann Arbor stage III/IV,, BM invasion, RLN invasion, DLN invasion, non-nasal type disease, two or more extranodal sites, elevated LDH levels, decreased ALB concentrations and positive EBV-DNA load. Furthermore, patients within the high LAR group exhibited a tendency towards higher PINK score, and indicated a more challenging course towards achieving CR following chemotherapy. In this study, 65.7% of the patients received the LVDP regimen, and it was observed that a higher proportion of patients in the low LAR group tended to receive the LVDP regimen, but the difference was not statistically significant.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline clinical characteristics divided by LAR\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh LAR (n\u0026thinsp;=\u0026thinsp;194)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow LAR (n\u0026thinsp;=\u0026thinsp;290)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.507\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e170(87.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e248(85.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42(14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.590\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e61 (31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e98(33.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e133 (68.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e192 (66.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG PS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e113(58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e275(94.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e81 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of B symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e144(74.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e116(40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50 (25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e174 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnn Arbor stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e97(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e259(89.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e97(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBM invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32(16.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e162(83.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e289 (99.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e109(56.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e91(31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e85(43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e199(68.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42 (21.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e152(78.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e272 (93.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary locations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasal type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e169(87.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e284(97.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-nasal type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25(13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6(2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePINK score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e110(56.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e264(91.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e84(43.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26(9.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtranodal sites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e118(60.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e273(94.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76(39.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17(5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy regimens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVDP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e106(54.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e212(73.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20(10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24(8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLIDE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35(18.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26(9.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP-GEMOX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14(7.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12(4.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19(9.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16(5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse after treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e83(42.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e218(75.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enon-CR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e111(57.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72(24.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; PINK, prognostic index of natural killer lymphoma; LVDP, L-asparaginase, etoposide, dexamethasone and cisplatin; LVP, L-asparaginase, vincristine and prednisone; GLIDE, gemcitabine, L-asparaginase; ifosfamide; dexamethasone and etoposide; P-GEMOX, pegaspargase, gemcitabine and oxaliplatin; CR, complete response\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOn the basis of LAR-associated prognostic score, patients were divided into three risk categories: low- risk (LDH\u0026thinsp;\u0026le;\u0026thinsp;230 u/L and ALB\u0026thinsp;\u0026ge;\u0026thinsp;40 g/L), intermediate-risk (LDH\u0026gt;230 u/L or ALB\u0026thinsp;\u0026lt;\u0026thinsp;40 g/L), and high- risk (LDH\u0026gt;230 u/L and ALB\u0026thinsp;\u0026lt;\u0026thinsp;40 g/L). In addition, among the three risk strata divided according to LAR-associated prognostic score, patients in the lower risk strata were more likely to receive the LVDP regimen, with an increasing tendency towards the lower end of the risk spectrum. Similar to LAR, notable differences in patient characteristics were found in different risk groups, with the exception of age and gender (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline clinical characteristics divided by LAR-associated prognostic score\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow risk (n\u0026thinsp;=\u0026thinsp;218)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntermediate risk (n\u0026thinsp;=\u0026thinsp;147)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;119)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e189(86.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e121(82.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e108(90.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26(17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11(9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.915\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e73 (33.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51(34.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e35(29.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e145 (66.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e96 (65.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e84(70.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG PS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e204(93.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e126(85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e58(48.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e61(51.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of B symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74(33.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e85(57.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e102(85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e144 (66.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62 (42.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17(14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnn Arbor stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e194(89.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e112(76.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50(42.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24(11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e69(58.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBM invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6(4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e27(22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e217(99.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e141 (95.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e92(77.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65(29.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66(44.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e70(58.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e153(70.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e81(55.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e49(41.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28(23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e205(94.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e127(86.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e91(76.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary locations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasal type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e213(97.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e136(92.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e98(82.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-nasal type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5(2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11(7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21(17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePINK score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e199(91.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e117(79.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e58(48.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17(8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30(20.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e61(51.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtranodal sites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e205(94.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e125(85.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e61(51.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13(6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22(15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e58(48.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy regimens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVDP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e157(72.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e98(66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e63(52.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16(7.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18(12.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10(8.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLIDE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22(10.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10(6.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e29(24.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP-GEMOX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9(4.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13(8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4(3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14(6.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8(5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13(10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse after treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e172(78.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e86(58.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e43(36.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enon-CR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46(21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61(41.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e76(63.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; PINK, prognostic index of natural killer lymphoma; LVDP, L-asparaginase, etoposide, dexamethasone and cisplatin; LVP, L-asparaginase, vincristine and prednisone; GLIDE, gemcitabine, L-asparaginase; ifosfamide; dexamethasone and etoposide; P-GEMOX, pegaspargase, gemcitabine and oxaliplatin; CR, complete response\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSurvival analysis and prognosis factors\u003c/h2\u003e \u003cp\u003eFollowing a median follow-up period of 70 months, spanning from 1 to 144 months, 47.7% (231 of 484) of the patients experienced disease progression or relapse, and 41.3% (200 of 484) of the patients had died. The estimated 5-year OS and PFS rates for these 484 patients were 58.7% and 52.0%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe univariate Cox regression analysis identified the following parameters with significant correlations to OS: ECOG PS (\u0026ge;\u0026thinsp;2), presence of B symptoms, Ann Arbor stage III/IV, non-nasal disease classification, BM invasion, RLN invasion, DLN invasion, non-CR response, elevated LDH concentrations (\u0026gt;230 u/L), decreased ALB levels (\u0026lt;\u0026thinsp;40 g/L), PINK score (\u0026ge;\u0026thinsp;2), high LAR (\u0026gt;5.4), and the LAR-associated prognostic score (Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Separate multivariate analyses were conducted incorporating LDH and ALB levels, the LAR, and the LAR-associated prognostic score. The findings indicated that advanced poor ECOG PS, RLN invasion and non-CR response after chemotherapy were adverse prognostic indicators. Of particular significance, LDH\u0026gt;230 u/L (p\u0026thinsp;=\u0026thinsp;0.003), ALB\u0026thinsp;\u0026lt;\u0026thinsp;40g/L (p\u0026thinsp;=\u0026thinsp;0.001), LAR\u0026gt;5.4 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and the LAR-associated prognostic score (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were substantially correlated with patient outcomes in ENKTL (Tables \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e,\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e,\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). The concordance statistic (C-index) for survival prediction was 0.70 (95% confidence interval (CI), 0.66\u0026ndash;0.73) using LDH and ALB classification, 0.67 (95% CI, 0.63\u0026ndash;0.70) using the LAR classification, and 0.70 (95% CI, 0.66\u0026ndash;0.73) using the LAR-associated prognostic score classification, respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analysis of overall survival\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRelative risk (95% CI), p value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026gt;60 years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.780 (0.505\u0026ndash;1.205),0.259\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.542 (1.124\u0026ndash;2.116),0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG PS (\u0026ge;\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.083 (2.263-4.200),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of B symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.838 (1.377\u0026ndash;2.455),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnn Arbor stage (III-IV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.972 (2.235\u0026ndash;3.952),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBM invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.387 (2.202\u0026ndash;5.208),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.068 (1.564\u0026ndash;2.735),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.924 (1.335\u0026ndash;2.773),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary locations (non-nasal type)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.392 (1.521\u0026ndash;3.761),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtranodal sites\u0026thinsp;\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.080 (2.276\u0026ndash;4.168),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse after treatment (non-CR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.688 (1.533\u0026ndash;1.858),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePINK score (\u0026ge;\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.960 (2.212\u0026ndash;3.960),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALB(\u0026lt;40 g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.943 (2.221\u0026ndash;3.917),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH(\u0026gt;230 u/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.880 (2.176\u0026ndash;3.813),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.253 (2.448\u0026ndash;4.332),\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAR-associated prognostic score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.256 (1.895\u0026ndash;2.687), \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; CR, complete remission; PINK, prognostic model for natural killer lymphoma; ALB, albumin; LDH, lactate dehydrogenase;LAR, lactate dehydrogenase to albumin ratio; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate analysis of overall survival according to LDH and ALB\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRelative risk (95% CI), p value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026gt;60 years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG PS (\u0026ge;\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.504 (1.019\u0026ndash;2.221), 0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of B symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnn Arbor stage (III-IV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBM invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.408 (1.047\u0026ndash;1.8093), 0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary locations (non-nasal type)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtranodal sites\u0026thinsp;\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse after treatment (non-CR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.592(1.422\u0026ndash;1.783), \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALB(\u0026lt;40 g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.731(1.244\u0026ndash;2.408), 0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH(\u0026gt;230 u/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.660 (1.185\u0026ndash;2.327), 0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; CR, complete remission; ALB, albumin; LDH, lactate dehydrogenase; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate analysis of overall survival according to LAR\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRelative risk (95% CI), p value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026gt;60 years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG PS (\u0026ge;\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of B symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnn Arbor stage (III-IV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBM invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.406 (1.046\u0026ndash;1.890), 0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary locations (non-nasal type)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtranodal sites\u0026thinsp;\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse after treatment (non-CR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.659 (1.484\u0026ndash;1.856), \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAR (\u0026gt;5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.182 (1.548\u0026ndash;3.075), \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; CR, complete remission; LAR, lactate dehydrogenase to albumin ratio; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate analysis of overall survival according to LAR-associated prognostic score\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRelative risk (95% CI), p value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026gt;60 years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG PS (\u0026ge;\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.496 (1.019\u0026ndash;2.197), 0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of B symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnn Arbor stage (III-IV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBM invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.406 (1.046\u0026ndash;1.889), 0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDLN invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary locations (non-nasal type)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtranodal sites\u0026thinsp;\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse after treatment (non-CR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.595 (1.426\u0026ndash;1.783), \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAR-associated prognostic score (\u0026gt;5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.696 (1.372\u0026ndash;2.096), \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eECOG PS, Eastern Cooperative Oncology Group performance status; BM, bone marrow; RLN, reginal lymph node; DLN, distant lymph node; CR, complete remission; LAR, lactate dehydrogenase to albumin ratio; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData on EBV-DNA were accessible for 345 individuals within this study. Our results revealed that PINK-E scores and EBV-DNA load were associated with prognosis in ENKTL patients with available EBV-DNA data (Supplementary table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Subsequently, we conducted additional analyses to assess the prognostic significance of LDH and ALB levels, the LAR, and the LAR-associated prognostic score within this group. Separate multivariate analyses were performed with LDH and ALB, the LAR, and the LAR-associated prognostic score. The findings indicated that the incorporation of EBV-DNA data in this patient subset substantiated the association of LDH and ALB levels, the LAR, and the LAR-associated prognostic score with patient outcomes. The relative risk associated with these factors remained consistent when compared to the entire cohort (Supplementary tables 3,4,5).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eThe prognostic significance of LAR and LAR-associated prognostic score\u003c/h2\u003e \u003cp\u003ePatients possessing low LAR demonstrated significantly better prognosis compared those with high LAR. The 5-year OS rates for patients in low LAR and high LAR groups were 69.6% and 36.3%, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Improved PFS was also found in patients with low LAR. The 5-year PFS rates for patients in low LAR and high LAR groups were 66.3% and 30.4%, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). According to LAR-associated prognostic score, patients were classified into low-risk, intermediate-risk, and high-risk groups. Significant differences on 5-year OS (low-risk versus (vs.) intermediate-risk, 77.4% vs. 55.0%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; low-risk vs. high-risk, 77.4% vs. 29.3%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; intermediate-risk vs. high-risk, 55.0% vs. 29.3%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA) and PFS (low-risk vs. intermediate-risk, 69.8% vs. 46.0%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; low-risk vs. high-risk, 69.8% vs. 26.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; intermediate-risk vs. high-risk, 46.0% vs. 26.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB) also have been identified.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor the 345 patients with available EBV-DNA data, the 5-year OS rates for patients in low LAR and high LAR groups were 73.7% and 58.5%, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; supplementary Fig.\u0026nbsp;1A), and the 5-year PFS patients in low LAR and high LAR groups were 65.8% and 33.7%, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, supplementary Fig.\u0026nbsp;1B). According to LAR-associated prognostic score, the 345 patients were also classified into low-risk, intermediate-risk, and high-risk groups. Significant differences on 5-year OS (low-risk vs. intermediate-risk, 79.1% vs. 57.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; low-risk vs. high-risk, 79.1% vs. 30.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; intermediate-risk vs. high-risk, 57.5% vs. 30.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; supplementary Fig.\u0026nbsp;2A) and PFS (low-risk vs. intermediate-risk, 70.9% vs. 48.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; low-risk vs. high-risk, 70.9% vs. 27.0%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; intermediate-risk vs. high-risk, 48.7% vs. 27.0%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; supplementary Fig.\u0026nbsp;2B) also have been identified.\u003c/p\u003e \u003cp\u003eUtilizing the PINK and PINK-E models, patients were categorized into three distinct risk groups, which exhibited significant differences in survival outcomes. Despite evaluating the PINK model, no significant distinction in survival outcomes was observed between the low-risk and intermediate-risk groups (p\u0026thinsp;=\u0026thinsp;0.792). Within this model, the 5-year OS rates were recorded at 66.1% for the low-risk group, 63.3% for intermediate-risk group, and 32.8% for the high-risk group. A similar pattern emerged when applying the PINK-E model, where no discernible difference was found between the low-risk and intermediate-risk groups (p\u0026thinsp;=\u0026thinsp;0.405). The 5-year OS rates for the PINK-E model were 69.6% for the low-risk group, 59.9% for the intermediate-risk group, and 31.6% for the high-risk group. We sought to further stratify the patients by separately integrating the LAR and LAR-associated prognostic score into the PINK and PINK-E models. In subgroup analyses within the low-risk and intermediate-risk as defined by the PINK system, the prognostic significance of the LAR and the LAR-associated prognostic score was demonstrated, revealing additional prognostic insights. The 5-year OS rates were 74.8% for the low LAR group and 54.6% for the high LAR group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). Furthermore, when stratified by the LAR-associated prognostic score into low-, intermediate-, and high-risk groups, the respective 5-year OS rates were 85.7%, 60.8%, and 41.3%, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB). Similarly, the LAR and LAR-associated prognostic score demonstrated enhanced capability in identifying survival disparities among patients categorized into the low-risk and intermediate-risk group according to the PINK-E index. The 5-year OS rates were 73.7% for the low LAR group and 39.7% for the high LAR group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eA). Additionally, when classified by the LAR-associated prognostic score into low-, intermediate-, and high-risk groups, the respective 5-year OS rates were 79.1%, 57.5%, and 30.7%, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrevious studies have established that LDH and ALB levels in patients with DLBCL hold substantial prognostic significance and can serve as valuable factors in clinical assessments of patient outcomes \u003csup\u003e[\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Furthermore, the LAR has emerged as a potential prognostic indicator in disease evaluation, albeit with scant data linking it specifically to DLBCL \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Our study marks the inaugural investigation into the correlation between the LAR and prognosis in ENKTL patients receiving asparaginase-based chemotherapy.\u003c/p\u003e \u003cp\u003eResearch indicates that ALB concentrations impact bodily metabolism, nutritional status, and the transport of substrates \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Additionally, the state of nutrition and inflammation can lead to a decrease in ALB synthesis, positioning ALB as an indicator of overall systemic nutrition and a straightforward measure of inflammatory response \u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. It is notable that ALB also plays a role in extending drug half-life and mitigating toxicity \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Due to diverse mechanisms related to the tumor itself, the host's reaction to the tumor, and the effects of anticancer treatments, malnutrition can lead to substantial complications for patients with malignancies\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. Persistent hypoproteinemia serves as a straightforward and potent indicator of poor prognosis in patients with DLBCL, and post-treatment follow-up should particularly attend to patients presenting with hypoalbuminemia \u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Integrating early alterations in ALB levels with established biomarkers has demonstrated potential to enhance the predictive accuracy of prognostic outcomes for patients with non-small cell lung cancer undergoing monotherapy with immune checkpoint inhibitors \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. The swift division of cancer cells is accompanied by a heightened rate of glucose consumption and irregular functioning of LDH, which is crucial for the metabolic process that transforms glucose into lactate \u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. Increased LDH levels predict adverse prognosis for hematologic malignancies, indicating a substantial tumor burden and aggressive disease course. Elevated serum LDH levels significantly influence the prognosis for achieving CR in patients with lymphoma. LDH is also recognized as one of the diagnostic criteria for various lymphoma prognostic systems.\u003c/p\u003e \u003cp\u003eThe LAR, a composite of LDH and ALB levels, offers a comprehensive assessment of the body's inflammatory response, nutritional status, and tumor burden, providing a holistic view of a patient's condition. Previous studies have demonstrated the association between LAR and prognosis in various malignancies \u003csup\u003e[\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e, establishing it as an independent poor prognostic factor. However, the prognostic significance of LAR in ENKTL has not yet been reported. This is the first study to evaluate the association between the LAR and prognosis in ENKTL patients receiving asparaginase-based therapy regimens.\u003c/p\u003e \u003cp\u003eAs there were no specific criteria for the optimal cutoff values of ALB and LDH, ROC analyses were conducted to determine these values for LDH, ALB, and LAR, which were found to be 230 u/L, 40 g/L, and 5.4, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multivariate analysis revealed that ALB\u0026thinsp;\u0026lt;\u0026thinsp;40 g/L, LDH\u0026gt;230 u/L and LAR\u0026gt;5.4, each independently correlated with poor prognostic outcomes for OS (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Our study revealed a significant difference in clinical outcomes between the high and low LAR groups. Specifically, patients in the high LAR group had worse 5-year OS and PFS, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB. Furthermore, our study identified significant differences in clinical manifestations and outcomes between patients with high LAR and those with low LAR. The high LAR group was more likely to exhibit unfavorable characteristics, such as poor ECOG PS, advanced disease stage, B symptoms, non-CR after chemotherapy etc. We proceeded to examine the significance of the LAR-associated prognostic score in ENKTL. Utilizing this scoring system, patients were categorized into three risk groups, determined by their serum LDH and ALB levels. A notable variation in prognostic outcomes were detected among patients classified into various risk groups, with higher scores correlating to adverse outcomes (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). Similar to LAR, patients with higher scores tended to have more unfavorable characteristics.\u003c/p\u003e \u003cp\u003eEBV-DNA serves as a significant biomarker for tumor burden, given that ENKTL tumor cells are persistently infected with the EBV. The diagnosis of ENKTL is confirmed by the presence of a positive viral titer through in situ hybridization. Additionally, the presence of EBV-DNA in peripheral blood is intimately linked to the survival rates and therapeutic outcomes for ENKTL patients \u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. The definitive threshold for the EBV-DNA titer remains unclear, with virtually all research considering a positive EBV-DNA status if any measurable concentration is present in the blood at diagnosis \u003csup\u003e[1,31\u0026ndash;33 ]\u003c/sup\u003e. In this study, 484 patients with ENKTL were included, among which 345 cases had available EBV data. We further analyzed the prognostic value of LAR in the population with available EBV data. Our findings showed a notable disparity in clinical outcomes between patients with high and low LAR values. Notably, those in the high LAR group exhibited poorer 5-year OS and PFS rates, as illustrated in Supplementary Fig.\u0026nbsp;1A and 1B. We advanced our investigation to assess the relevance of the LAR-associated prognostic score among ENKTL patients with accessible EBV-DNA data. With the application of this scoring system, participants were divided into three distinct risk groups. Significant differences in prognostic outcomes were observed among these groups, with higher scores indicating a correlation with unfavorable outcomes, as depicted in Supplementary Figs.\u0026nbsp;2A and 2B.\u003c/p\u003e \u003cp\u003eThe PINK and PINK-E models are referred as novel prognostic scoring systems for ENKTL \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. In both the PINK and PINK-E classification systems, the outcomes between the low-risk and intermediate-risk groups did not exhibit significant differences. When the LAR and LAR-associated prognostic score were applied separately to evaluate the low-risk and intermediate-risk groups defined by the PINK system, substantial variations in survival rates were noted. These differences were evident between the groups with low versus high LAR values, as well as across the categorized low-, intermediate-, and high-risk groups based on the LAR-associated prognostic score. Applying the LAR and LAR-associated prognostic score to assess the low-risk and intermediate-risk groups in the PINK-E system yielded comparable findings.\u003c/p\u003e \u003cp\u003eThere were some limitations in this study. Firstly, this study represents a single-center analysis, and its findings necessitate further validation across diverse populations to ensure broader applicability and reliability. Secondly, the retrospective design of this study could have potentially led to the introduction of selection bias and information bias. Therefore, future prospective studies are needed to validate our results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe present study is the first to demonstrate the prognostic value of the LAR and LAR-associated prognostic score in patients with ENKTCL. The findings indicate that both LAR and LAR-associated prognostic score are correlated with the outcomes of patient with ENKTCL, and they notably enhance the precision of prognostic assessment, thereby improving the efficacy of clinical decision-making.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe novel findings of this study are detailed within the article and its supplementary materials. For additional inquiries or clarifications, readers should contact the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no financial support was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in this study were approved by the institutional review boards (IRB) at West China Fourth Hospital, Sichuan University and in accordance with the ethical standards of the institutions and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Due to the retrospective nature of this study, informed consent was not required by the IRB at West China Fourth Hospital, Sichuan University.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors state that no commercial or financial interests influenced the research, eliminating any potential conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKim SJ, Yoon DH, Jaccard A, et al. A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis. Lancet Oncol. 2016;17:389-400.\u003c/li\u003e\n\u003cli\u003eTse E, Kwong YL. How I treat NK/T‐cell lymphomas. Blood. 2013;121(25):4997-5005.\u003c/li\u003e\n\u003cli\u003eYamaguchi M, Kita K, Miwa H, et al. Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells. 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Prognostic significance of preoperative lactate dehydrogenase to albumin ratio in breast cancer: a retrospective study. Int J Gen Med.2023;16:507-514.\u003c/li\u003e\n\u003cli\u003eWu WK, Miao L, Zhao LD, et al. Prognostic value of lactate dehydrogenase, serum albumin and the lactate dehydrogenase/albumin ratio in patients with diffuse large B-cell lymphoma. Hematology. 2024;29(1):2293514. \u003c/li\u003e\n\u003cli\u003eHu X, Feng X, Wang H, et al. Association between serum albumin levels and survival in elderly patients with diffuse large B-cell lymphoma: a single-center retrospective study. Transl Cancer Res. 2023;12(6):1577-1587.\u003c/li\u003e\n\u003cli\u003eWei X, Zheng J, Zhang Z, et al. Consecutive hypoalbuminemia predicts inferior outcome in patients with diffuse large B-cell lymphoma. Front Oncol. 2021;10:610681.\u003c/li\u003e\n\u003cli\u003eBakirtas M, Basci S, Candır BA, et al. 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Mol Asp Med. 2012;33(3):209-290. \u003c/li\u003e\n\u003cli\u003eGhuman J, Zunszain PA, Petitpas I, et al. Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol. 2005;353(1):38-52.\u003c/li\u003e\n\u003cli\u003evon Meyenfeldt M. Cancer-associated malnutrition: an introduction. Eur J Oncol Nurs. 2005;9(Suppl 2):S35-S38.\u003c/li\u003e\n\u003cli\u003eKaneko H, Shimura K, Yoshida M, et al. Serum albumin levels strongly predict survival outcome of elderly patients with diffuse large B-cell lymphoma treated with rituximab-combined chemotherapy. Int J Hematol Oncol Stem Cell Res. 2022;16(1):1-8.\u003c/li\u003e\n\u003cli\u003eGuo Y, Wei L, Patel SH, et al. Serum albumin: early prognostic marker of benefit for immune checkpoint inhibitor monotherapy but not chemoimmunotherapy. Clin Lung Cancer. 2022;23(4):345-355.\u003c/li\u003e\n\u003cli\u003ede la Cruz-L\u0026oacute;pez KG, Castro-Mu\u0026ntilde;oz LJ, ReyesHern\u0026aacute;ndez DO, et al. Lactate in the regulation of tumor microenvironment and therapeutic approaches. Front Oncol. 2019;9:1143.\u003c/li\u003e\n\u003cli\u003eKim HS, Kim KH, Kim KH et al. Whole blood Epstein\u0026ndash;Barr virus DNA load as a diagnostic and prognostic surrogate: extranodal natural killer/T-cell lymphoma. Leuk. Lymphoma. 2009; 50, 757-763.\u003c/li\u003e\n\u003cli\u003eIto Y, Kimura H, Maeda Y et al. Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type. Clin. Cancer Res. 2012;18, 4183-4190.\u003c/li\u003e\n\u003cli\u003eChan KCA, Zhang J, Chan ATC et al. Molecular characterization of circulating EBV DNA in the plasma of nasopharyngeal carcinoma and lymphoma patients. Cancer Res.2003; 63(9), 2028\u0026ndash;2032.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Extranodal natural killer/T-cell lymphoma, lactate dehydrogenase, albumin, lactate dehydrogenase/albumin ratio, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-5503269/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5503269/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eExtranodal natural killer/T-cell lymphoma (ENKTL) is recognized for its aggressive nature and variable clinical presentation, often leading to a poor prognosis. While the combined assessment of baseline serum lactate dehydrogenase (LDH) and albumin (ALB) levels has demonstrated prognostic value across various malignancies, its specific application and evidence in ENKTL are unstudied.\u003c/p\u003e\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThis study aimed to investigate the impact of the lactate dehydrogenase/albumin ratio (LAR) in ENKTL, offering nutritional and immunological insights to enhance risk stratification.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective analysis of 484 ENKTL patients treated with asparaginase-based regimens. The optimal thresholds for serum LDH and ALB levels were identified as 230 u/L and 40 g/L, respectively, and 5.4 for LAR. With a median follow-up of 70 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were determined to be 58.7% and 52.0%, respectively. Patients with higher LAR values exhibited more unfavorable clinical features and poorer 5-year OS and PFS rates compared to those with lower LAR values. Utilizing the LAR-associated prognostic score, patients were categorized into distinct risk groups, revealing significant differences in 5-year OS and PFS among these groups. By integrating the LAR and LAR-associated prognostic score into the prognostic index for natural killer lymphoma (PINK) and PINK with Epstein-Barr virus (PINK-E) models, we found that these measures provided additional prognostic information.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eElevated LDH and decreased ALB levels at the time of initial diagnosis are indicative of a poor prognosis in ENKTL patients. The LAR and LAR-associated prognostic score may serve as independent prognostic indicators for ENKTL, potentially aiding in risk stratification and informing clinical decision-making.\u003c/p\u003e","manuscriptTitle":"The prognostic value of lactate dehydrogenase/albumin ratio in extranodal natural killer/T cell lymphoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-07 12:42:24","doi":"10.21203/rs.3.rs-5503269/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-02T20:01:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-22T05:47:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"301616789983599361792325578954993296843","date":"2025-04-10T03:54:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-05T02:00:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"327958770765033632454656481379196304750","date":"2025-04-05T01:34:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-04T16:35:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-04T10:28:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-04-04T09:39:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c01eb234-6f80-4629-a942-4635f826c083","owner":[],"postedDate":"April 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-21T16:01:25+00:00","versionOfRecord":{"articleIdentity":"rs-5503269","link":"https://doi.org/10.1186/s12885-025-14393-5","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2025-07-15 15:57:32","publishedOnDateReadable":"July 15th, 2025"},"versionCreatedAt":"2025-04-07 12:42:24","video":"","vorDoi":"10.1186/s12885-025-14393-5","vorDoiUrl":"https://doi.org/10.1186/s12885-025-14393-5","workflowStages":[]},"version":"v1","identity":"rs-5503269","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5503269","identity":"rs-5503269","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}