Long-term survival of extranodal NK/T-cell lymphoma: a single-center real- world study of 408 cases in China

Long-term survival of extranodal NK/T-cell lymphoma: a single-center real- world study of 408 cases in China | 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 Long-term survival of extranodal NK/T-cell lymphoma: a single-center real- world study of 408 cases in China Jie Wang, Yunfan Yang, Chunlan Zhang, Xushu Zhong, Qinyu Liu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5768765/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aims To investigate the long-term survival of extranodal NK/T-cell lymphoma (ENKTL) before the era of new drugs. Methods This retrospective real-world study enrolled patients with ENKTL at xx hospital between January, 2012 and December, 2017. Survival analysis and multivariate Cox proportional hazard regression analysis were performed. Results Among 408 patients with ENKTL, the 5-year overall survival (OS) was 75.3%, and 5-year progression-free survival (PFS) was 75.3%. Nasal type had significantly better 5-year OS (78.8%) and PFS (78.8%) compared to extranasal type (45.1% and 45.6%, respectively; P < 0.001). Early-stage patients had higher 5-year OS (84.5%) and PFS (91.2%) with chemotherapy plus radiotherapy compared to chemotherapy alone (56.7% and 85.9%, respectively; P < 0.001). Asparaginase-based regimens improved outcomes, especially in advanced stages. Achieving complete remission (CR) after first-line treatment significantly improved 5-year OS (81.9%) and PFS (82.0%). Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) (HR = 2.728, 95%CI: 1.563–4.761); type of first-line treatment, including chemotherapy and radiotherapy (HR = 0.303, 95%CI: 0.184–0.501), chemotherapy and ASCT (HR = 0.373, 95%CI: 0.162–0.857), and first-line treatment achieved CR (HR = 0.565, 95%CI: 0.364–0.877), were independent prognostic factors for patients’ OS. Conclusions Different treatment strategies might impact the long-term survival of patients with ENKTL before the era of new drugs. Chemotherapy combined with radiotherapy, asparaginase-based regimens, and achieving complete remission (CR) after first-line treatment are associated with improved outcomes, particularly in early-stage and advanced-stage patients. Moreover, ECOG performance status, type of first-line treatment were independent prognostic factors for OS. Extranodal NK/T-cell lymphoma Chemotherapy Radiotherapy Survival analysis Real world study Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Extranodal NK/T-cell lymphoma (ENKTL) is a rare aggressive lymphoma, which was formally included in the WHO classification of hematopoietic and lymphoid tumors in 1999 and updated in 2022 [ 1 , 2 ]. This disease exhibits a distinct geographical distribution, with a lower prevalence in Europe and North America compared to a higher incidence in East Asia and Central and South America [ 3 , 4 ]. The exact etiology of ENKTL remains unclear, but it is strongly associated with Epstein-Barr (EB) virus infection, a factor that is not geographically confined [ 5 ]. Clinically, ENKTL is characterized by its aggressive nature and resistance to conventional anthracycline-based chemotherapy [ 6 ], leading to a generally poor prognosis. Radiation therapy has emerged as a critical component in the management of localized ENKTL, offering significant benefits in controlling localized lesions [ 7 ]. However, extranasal involvement and advanced disease stages are major prognostic factors associated with poorer outcomes [ 5 , 8 , 9 ]. Data from a previous international peripheral T-cell lymphoma project [ 5 ] revealed that the median progression-free survival for the entire ENKTL cohort was only 6 months, with an overall survival of just 8 months, making it the subtype with the worst survival outcomes among all T-cell lymphomas [ 10 ]. Notably, the majority of these cases were nasal in origin. In recent years, the therapeutic landscape for ENKTL has evolved, with growing evidence supporting the use of concurrent or sequential radiotherapy combined with anthracycline-free chemotherapy for localized lesions [ 6 , 11 ]. For advanced-stage and relapsed or refractory ENKTL, non-anthracycline-based chemotherapy regimens, particularly those incorporating L-asparaginase, have shown promise [ 12 – 15 ]. A recent international study reported a 5-year overall survival rate of 54% for nasal-type ENKTL and 34% for extranasal-type ENKTL [ 16 ]. This study aims to evaluate the prognosis and treatment outcomes of patients with ENKTL through an examination of their clinical characteristics and survival data. Specifically, the study focuses on the impact of various treatment strategies on clinical outcomes in the pre-new drug era. Methods Study design and patients This study originated from an international multicenter, hospital-based case-control study of lymphoma in Asia, which was initiated in 2012.Within this broader project, this retrospective real-world study enrolled patients with ENKTL at West China Hospital Affiliated to Sichuan University between January, 2012 and December, 2017. Patient enrollment conditions were based on local histologic diagnosis. Inclusion criteria: 1) Patients must be 18 years of age or older. 2) Adequate tissue biopsies must be available for diagnosis and classification. 3) Comprehensive clinical data, including baseline information on disease stage and laboratory ancillary tests at diagnosis, must be available. 4) Detailed records of the type of treatment received must be documented. 5) Patients must have at least 5 years of follow-up data. Those with incomplete data were excluded. The study was approved by the Ethics Committee on Biomedical Research of our hospital, and all patients provided written informed consent prior to study entry. Data collection and definitions The first ENKTL patient was enrolled in the program on January 28, 2012, and the last patient was enrolled on December 29, 2017. According to the World Health Organization (WHO) 2008 classification, previously untreated ENKTL patients at our hospital were enrolled to receive any treatment. The treatment strategy involves radiotherapy, chemotherapy and autologous hematopoietic stem cell transplantation. As this was a retrospective study, there were many specific chemotherapy schemes. The chemotherapy schemes were divided into two categories, including with/without asparaginase. Further subdivided into 7 types, including L-asparaginase+, platinum+, gemcitabine-; L-asparaginase+, platinum-, gemcitabine+; L-asparaginase+, platinum+, gemcitabine+; L-asparaginase+, platinum-, gemcitabine-; L-asparaginase-, platinum+, gemcitabine+; L-asparaginase-, platinum+, gemcitabine-; and L-asparaginase-, platinum-, gemcitabine-. Data were collected on baseline clinical and disease characteristics, Eastern Cooperative Oncology Group (ECOG) performance status, first-line treatment and response assessment, and updated survival follow-up. Additionally, we analyzed the ENKTL cohort using the PINK-E index. This index incorporates EBV-DNA positivity into the Prognostic Index of Natural Killer Lymphoma (PINK) score, first published in 2016, and includes five risk factors: age >60 years, stage III or IV, distant lymph node involvement, extranasal lesions, and EBV-DNA positivity [17]. According to the prognostic index, patients were categorized into three groups: low-risk (0-1 risk factors), intermediate-risk (2 risk factors), and high-risk (≥3 risk factors). Outcomes The primary outcome was 5-year overall survival (OS), and the secondary outcome was 5-year progression-free survival (PFS). Other predefined endpoints included the proportion of patients who achieved remission after initial treatment. OS was defined as the time from diagnosis to death from any cause, or the date of the last known contact for living patients. PFS was defined as the time from diagnosis to disease progression or death due to lymphoma. Statistical analysis Statistical analyses were performed using SPSS Statistics for Windows, Version 19.0 (Armonk, NY: IBM Corp.) and R software (version 4. 0.3; http://www. R-project. org). Categorical variables were presented as numbers (percentages). Differences in categorical variables were analyzed using the χ² test. Continuous variables were dichotomized using MaxStat analysis (Maximally Selected Rank Statistics). The Cox proportional hazards model was used to analyze the univariable association between prognostic factors and overall survival (OS). All variables with P < 0.05 in the univariable analysis were included in the multivariable analysis. Forward selection was used to identify the best predictor set, and the Akaike Information Criterion (AIC) was employed to evaluate the model fit. Kaplan-Meier analysis was used to estimate survival outcomes, and the log-rank test was performed to compare differences between groups. All statistical tests were two-sided, and statistical significance was set at P < 0.05. Results As of the data cut-off date (January 1, 2018), 408 patients were enrolled for analysis. Of these cases, 347 (85%) were defined as nasal and 61 (15%) were defined as extranasal type. Table 1 shows the baseline clinical characteristics of the patients. As expected, patients with extranasal type showed more adverse clinical features than nasal type, especially in ECOG performance status, lactate dehydrogenase (LDH), stage III-IV, PINK-E score, bone marrow involvement, and distant lymph node involvement (all P < 0.05). At a median OS follow-up of 56.0 months (95% CI 51.8-60.2), all ENKTL patients (n=408) had a 3-year OS of 79.2% and a 5-year OS of 75.3% ( Figure 1A ). In patients with nasal type, the 5-year OS was 78.8 %, which was significantly higher than that in patients with extranasal type (45.1%), and the difference was statistically significant (P < 0.001) ( Figure 1C ). At a median PFS follow-up of 55. 0 months (95 % CI 50.8-59.2), the 3-year PFS of all ENKTL patients was 77.8 %, and the 5-year PFS was also 75.3% ( Figure 1B ). The 5-year PFS of patients with nasal type was 78. 8%, which was significantly higher than that of patients with extranasal type (45.6 %) (P < 0.001) ( Figure 1D ). According to the Ann Arbor stage, the 5-year OS and 5-year PFS of patients with early stage (stage I and II) were 83.0 % and 90.9 %, respectively, while the 5-year OS and 5-year PFS of patients with advanced stage (stage III and IV) were 53.5 % and 73.5 %, respectively, both with statistically significant differences (P < 0.001) ( Figure 2A and B ). From the available data, the PINK-E score could be calculated for 408 cases. Among them, 75 cases (18.4 %) were classified as low-risk group, 188 cases (46.1 %) as medium-risk group, and 145 cases (35.5 %) as high-risk group. The 5-year OS was 89. 6% in the low-risk group, 81.2% in the intermediate-risk group, and 57.8% in the high-risk group (P < 0.001; Figure 2C ). The 5-year PFS was 89.7% in the low-risk group, 81. 1% in the intermediate-risk group, and 57.8 % in the high-risk group, with statistically significant differences (P < 0.001; Figure 2D ). Of the 408 patients analyzed, 280 (68.6%) patients received chemotherapy and radiotherapy as first-line treatment and 24 (5.9%) patients received chemotherapy and ASCT consolidation as first-line treatment ( Table 1 ). Among the regimens containing asparaginase used in 378 patients, VDLP regimen (L-asparaginase, cisplatin, dexamethasone and etoposide) was the most commonly used, implemented in 229 (60. 6%) patients and used mainly in the combination of radiotherapy and chemotherapy in patients with early ENKTL; followed by the GLIDE regimen (gemcitabine, etoposide, ifosfamide, L-asparaginase and dexamethasone), implemented in 103 (27. 4%) patients and used mainly for chemotherapy in patients with advanced ENKTL; other asparaginase-containing regimens include P-GemOx (pegaspargase, gemcitabine and oxaliplatin), DDGP (dexamethasone, cisplatin, gemcitabine and pegaspargase), AspaMetDex (L-asparaginase, methotrexate and dexamethasone), etc. For early-stage (stages I and II) patients receiving chemotherapy alone (n = 27), the 3-year OS was 56.7 %, the 5-year OS was 56.7 %, the 3-year PFS was 85.9 %, and the 5-year PFS was 85.9 %. In contrast, for early-stage patients (n=249) who received the combination of chemotherapy and radiotherapy, the 3-year OS was 88.6 %, the 5-year OS was 84.5 %, the 3-year PFS was 91.2 %, and the 5-year PFS was 91.2 % ( Figure 3A and B ), and the combination of chemotherapy and radiotherapy was significantly better than that of patients who received chemotherapy alone. For advanced-stage (stage III and IV) patients receiving chemotherapy alone (n = 66), 3-year OS was 41.5 %, 5-year OS was 34.7 %, 3-year PFS was 73.0%, and 5-year PFS was 73.0 %. In contrast, among patients with advanced disease who received chemotherapy and radiotherapy (n=31), 3-year OS was 85.9 %, 5-year OS was 80.2 %, 3-year PFS was 82.6 %, 5-year PFS was 82.6%; among patients who received chemotherapy and ASCT (n=21), 3-year OS was 63.3 %, 5-year OS was 63.3 %, 3-year PFS was 65.6 %, and 5-year PFS was 65.6 % ( Figure 3C and D ). We then explored the effects of different chemotherapy regimens on survival outcomes of ENKTL. Classified by chemotherapy regimens, all patients receiving asparaginase-based regimens had 5-year PFS of 87.0% and 5-year OS of 75.2%, while those receiving asparaginase-free regimens had 5-year PFS of 92.9% and 5-year OS of 63.8%. For early-stage patients, the 5-year PFS was 90. 9 % and the 5-year OS was 83. 0 % for the asparaginase-based regimen versus 91.7 % and 73.4 % for the asparaginase-free regimen ( Figure 4A and B ). For advanced-stage patients, the 5-year PFS of the asparaginase-based regimen was 54. 6 % and the 5-year OS was 54.7 %, while the 5-year PFS of the asparaginase-free regimen was 0.0 % and the 5-year OS was 0.0 % ( Figure 4C and D ), the differences were statistically significant. There were also differences in the treatment response of different chemotherapy regimens based on asparaginase ( Figure 5 ). Overall, 250 (61.3%) of 408 patients (including 223 nasal and 27 extranasal) achieved CR after first-line treatment, with the 5-year OS of 81.9% (85.5% nasal and 48.6% extranasal), and 5-year PFS of 82.0% (85.5% nasal and 48.9% extranasal). In contrast, patients who did not achieve CR with first-line therapy had significantly poorer outcomes, with the 5-year OS of 63.2% and 5-year PFS of 63.0% ( Figure 6 and Figure 7 ). The effects of various factors on the survival of patients were analyzed. The results of univariate analysis of Cox regression model showed that nasal type, ECOG, LDH, B symptoms, Ann Arbor stage, PINK-E score, bone marrow involvement, distant lymph node involvement, first-line treatment, whether first-line treatment achieved CR were risk factors for patient prognosis, with statistically significant differences (P < 0.05). Multivariate analysis showed that ECOG (HR=2.728, 95%CI: 1.563-4.761, P < 0.001); type of first-line treatment, including chemotherapy and radiotherapy (HR=0.303, 95%CI: 0.184-0.501, P < 0.001), chemotherapy and ASCT (HR=0.373, 95%CI: 0.162-0.857, P = 0.020), and first-line treatment achieved CR (HR=0.565, 95%CI: 0.364-0.877, P = 0.011), were independent prognostic factors for patients’ OS ( Table 2 ). Discussion This study demonstrated that different treatment strategies might impact the long-term survival of patients with ENKTL before the era of new drugs. Chemotherapy combined with radiotherapy, asparaginase-based regimens, and achieving complete remission (CR) after first-line treatment are associated with improved outcomes, particularly in early-stage and advanced-stage patients. Moreover, ECOG performance status, type of first-line treatment were independent prognostic factors for OS. These findings highlight the importance of tailored treatment approaches in managing ENKTL. To our knowledge, this paper presents the largest study to date of patients with ENKTL before the era of new drugs. A total of 408 patients with NK/T-cell lymphoma were enrolled in the lymphoma project launched in 2012. Compared to the International Peripheral T-cell Lymphoma Program reported in 2009 (including 136 patients with ENKTL from 1990 to 2002 from 22 centers in 13 countries) [5]. We found that the survival rate of ENKTL patients was significantly improved, representing the largest change in clinical outcomes among all T-cell lymphoma subtypes studied in the past decade. This improvement may be attributed to the evolution of clinical regimens, including a shift from anthracycline-based therapy to asparaginase-based and platinum-based regimens and the increasing use of radiotherapy. In this study, the improvement of survival rate was significantly correlated with ECOG score, EBV-DNA quantification, baseline Hb and PLT, and CR in first-line treatment. In the entire ENKTL cohort, we observed a similar proportion of extranasal cases (61 cases in 15%) as previously reported in population-based studies. As expected, survival rates were significantly lower in patients with extranasal type than in patients with nasal type. Consistent with this result, advanced-stage (stage III and IV) patients had a significantly worse prognosis than early-stage (stage I and II) patients. Although the prognostic prediction of ENKTL is not straightforward, distinguishing between early and advanced stage is crucial for treatment a planning and prognosis [18]. In 2016, the ENKTL-specific prognostic index PINK was described, and the score showed a better prognostic description in the context of non-anthracycline therapy [17]. This score was further refined in advanced disease to include detectable Epstein-Barr virus DNA in peripheral blood as an additional parameter (PINK-E) [17]. We validated the PINK-E score in the ENKTL cohort and confirmed that a high-risk PINK score can identify patients with a particularly poor prognosis. Prospective studies of rare malignancies like NK/T-cell lymphoma are essential to improve understanding of the epidemiological and clinical factors affecting the course of the disease and to provide information on treatment patterns and survival outcomes. Our ENKTL dataset has both strengths and limitations as a single-center study. The study centrally registers data from patients with ENKTL diagnosed over 6 consecutive years at the largest single-center size hospital in China, allowing insight into the clinical features of ENKTL and providing measures of its modern clinical treatment. Moreover, the long-term follow-up of the study made the data on survival outcomes trustworthy. However, the size and scope of single-center data is also somewhat restrictive. Professor Au [5] reported in 2009 an international peripheral T-cell lymphoma retrospective project in which 136 (11.8%) of 1153 newly diagnosed peripheral T-cell lymphoma adult cases from 1990-2002 in 22 centers in 13 countries were ENKTL (68% nasal, 26% extranasal and 6% unclassifiable). The statistical prevalence was higher in Asian countries than in Western countries (22% and 5%) and higher in mainland Asia than in Japan (34%-56% and 11%). As expected, the survival outcome of extranasal type was significantly worse than that of nasal type, and consistent with this result, prognosis was significantly worse in advanced stage than in early stage. The median OS and PFS of the entire cohort were only 0.65 years and 0.48 years (7.8 and 5.8 months), respectively, which was the worst survival rate of all PTCLs in the project. Except for those with early-stage nasal diseases, survival rates of more than 1 year are not common. Recently, a study of the International T-cell Lymphoma Project showed [16] that 166 patients were diagnosed with ENKTL and during the median follow-up of 44 months, the 5-year overall survival rate of nasal patients (n = 98) was 54 %, and that of extranasal patients (n = 68) was 34 %. The 5-year overall survival rate was 55% for stage I patients, 42% for stage II patients, and 24 % for stage III~IV patients. In our study, the 5-year overall survival was 78.8 % in patients with nasal type and 45.1 % in patients with extranasal type. The 5-year OS of patients with stage I and II was 83. 0 %, and that of patients with stage III and IV was 53.5 %. The significant improvement in PFS and OS represents a paradigm shift in the clinical management of patients with ENKTL. The principles of treatment for early and advanced disease in ENKTL differ, with early stages being treated with a combination of radiotherapy and chemotherapy, while advanced stages are dominated by chemotherapy, with residual lesions being considered for local and radiotherapy, and patients with advanced disease who achieve high-quality remission may benefit from autologous transplantation [19]. In the past decade, significant differences in treatment modalities include a significant decline in the proportion of patients receiving anthracyclines, and a corresponding increase in the proportion of patients receiving platinum or asparaginase. Prospective clinical studies have shown the important prognostic value of asparaginase in ENKTL treatment regimens [12, 14], and radiotherapy combined with asparaginase chemotherapy has become the cornerstone of initial treatment for patients with early-stage ENKTL [20]. Our study emphasizes the important role of radiotherapy in the treatment of ENKTL. In patients with early disease, the combination of chemotherapy and radiotherapy was associated with improved survival (5-year survival rate was 845 %), and chemotherapy alone was associated with poor prognosis (5-year survival rate was 56.7 %). The sequence of radiotherapy and chemotherapy in ENKTL includes sequential chemoradiotherapy, concurrent chemoradiotherapy and ' sandwich ' therapy. Currently, chemotherapy sequential radiotherapy is a common mode. In previous studies, the 5-year PFS and OS rates of early-stage ENKTL patients receiving sequential radiotherapy chemoradiotherapy were 64%~83% and 64%~89%, respectively, and most of them were treated with chemotherapy followed by radiotherapy [21]. Concurrent radiotherapy is common in Japan and Korea, but rare in other countries, and some studies suggest that concurrent radiotherapy is equivalent to sequential radiotherapy [22]. 'Sandwich ' therapy refers to radiotherapy after 2~3 cycles of chemotherapy (50~56 Gy, 25~28 times a day, 5 times a week), followed by 2~3 consolidation cycles of chemotherapy. Professor Zou Liqun 's team at our hospital reported that the ' sandwich ' therapy achieved an CR rate of 80. 8%~83. 3% for early stage ENKTL, with both 5-year PFS and OS rates of 64 % [ 23,24 ]. However, the potential impact of different chemotherapy regimens on radiotherapy efficacy and dose requirements is still not well defined. For advanced-stage patients, asparaginase-containing chemotherapy is the most effective systemic chemotherapy. The SMILE [20, 25] and AspaMetDex regimens recommended by the NCCN guidelines are highly effective [12], but the toxicity is also obvious. The P-GemOx regimen is a simple and cost-effective option with manageable toxicities [26]. Dr. Ji Jie from our hospital previously reported that the GLIDE regimen (gemcitabine, asparaginase, ifosfamide, dexamethasone, and etoposide) was used to treat 42 patients with newly diagnosed advanced and relapsed refractory ENKTL, and 31 patients (73.8 %) achieved CR, of whom 14 patients received sequential ASCT, with 1-year PFS and OS rates of 656% and 827%, respectively, and 4-year PFS and OS rates were 48. 2% and 63. 1%, respectively [27, 28]. In this study, the chemotherapy regimens containing asparaginase were divided into the following 7 categories: (i) asparaginase+, platinum+, gemcitabine- (advanced-stage, mainly VDLP regimen); (ii) asparaginase+, platinum-, gemcitabine+ (advanced-stage, mainly GLIDE regimen); (iii) asparaginase+, platinum+, gemcitabine+ (advanced-stage, mainly DDGP); (iv) asparaginase+, platinum-, gemcitabine- (advanced-stage, mainly AspaMetDex regimen); (v) L-asparaginase-, platinum+, gemcitabine+; (vi) L-asparaginase-, platinum+, gemcitabine-; (vii) L-asparaginase-, platinum-, gemcitabine-. Among them, the second category of chemotherapy regimen containing asparaginase and gemcitabine as the first-line treatment had the highest CR rate of 40 % in advanced-stage ENKTL, followed by the first category of chemotherapy regimen containing asparaginase and platinum (CR rate was 28.6 %). Moreover, multivariate analysis identified several independent prognostic factors for overall survival (OS) in patients with extranodal NK/T-cell lymphoma (ENKTL). Specifically, ECOG performance status was a significant predictor of worse outcomes, consistent with findings from previous studies [29, 30]. Poor performance status often reflects a higher tumor burden and systemic involvement, which can negatively impact treatment tolerance and efficacy [31]. The type of first-line treatment was also a critical factor. Patients receiving chemotherapy combined with radiotherapy and chemotherapy followed by autologous stem cell transplantation (ASCT) had significantly better OS. This finding aligns with the current consensus that multimodal therapy, particularly the combination of chemotherapy and radiotherapy, is essential for optimal outcomes in ENKTL [32, 33]. Radiotherapy is particularly effective in controlling localized disease, while chemotherapy addresses systemic disease and reduces the risk of distant metastasis [34]. Achieving complete remission (CR) after first-line treatment was another independent prognostic factor. This is consistent with the literature, which emphasizes the importance of achieving CR in improving long-term survival in lymphomas [35, 36]. Early and complete eradication of the disease can prevent the development of resistant clones and reduce the likelihood of relapse. These findings underscore the importance of a comprehensive and individualized approach to treating ENKTL. Tailoring treatment strategies based on patient characteristics and disease stage can significantly improve outcomes. Future research should focus on optimizing treatment protocols and identifying biomarkers to further personalize therapy. Strengths and Limitations This study utilizes real-world data from a substantial cohort of 408 patients, providing valuable insights into the clinical practices and outcomes associated with the treatment of extranodal natural killer/T-cell lymphoma (ENKTL) in a practical setting. It encompasses a comprehensive analysis of various treatment strategies, clinical characteristics, and survival outcomes, thereby facilitating a thorough understanding of the factors influencing patient prognosis. The application of multivariate Cox proportional hazards regression analysis allowed for the identification of independent prognostic factors, yielding robust and reliable findings. With a median follow-up of 56.0 months for overall survival (OS) and 55.0 months for progression-free survival (PFS), the study presents long-term survival data that are critical for evaluating the effectiveness of different treatment strategies. Furthermore, subgroup analyses based on disease stage, type of first-line treatment, and PINK-E score provide a nuanced understanding of how these factors impact patient outcomes. Nevertheless, this study is subject to certain limitations. First, it was conducted at a single center, which may limit the generalizability of the findings to other populations or regions characterized by differing clinical practices and patient demographics. Second, the study is situated in the pre-new drug era, suggesting that the results may not be directly applicable to the contemporary treatment landscape, which now includes newer agents and therapies. Third, despite the implementation of multivariate analysis, there may still exist unmeasured confounding factors that could affect the results. Finally, variability in treatment regimens and dosing among different patients may influence the comparability of the outcomes, although efforts were made to standardize treatment protocols to the greatest extent possible. Despite these limitations, this study offers significant insights into the long-term survival and treatment outcomes of ENKTL, underscoring the necessity for tailored and multidisciplinary approaches in the management of this aggressive lymphoma. Conclusions This study demonstrated that various treatment strategies might have significantly influence on the long-term survival of patients with ENKTL prior to the introduction of novel pharmacological agents. The combination of chemotherapy and radiotherapy, asparaginase-based regimens, and the achievement of CR following first-line treatment were associated with improved outcomes, particularly among both early-stage and advanced-stage patients. Furthermore, the ECOG performance status and the nature of the first-line treatment emerged as independent prognostic factors for OS. These findings underscore the importance of personalized treatment approaches in the management of ENKTL. Abbreviations ENKTL: extranodal NK/T-cell lymphoma; OS: overall survival; PFS: progression-free survival; CR: complete remission; ECOG: Eastern Cooperative Oncology Group; WHO: World Health Organization; PINK: Prognostic Index of Natural Killer Lymphoma; AIC: Akaike Information Criterion; Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee on Biomedical Research of our hospital. Consent for publication All patients provided written informed consent prior to study entry. Availability of data and materials Not applicable Competing Interests Not Applicable. Funding Sichuan Science and Technology Department for Key Research and Development projects (2019YFS0027) Authors' contributions JW conceived the study and played the primary role in data analysis, as well as the drafting of the manuscript and. YFY, CLZ, XSZ, JX, WJT and QYL have made a substantial contribution to the data collation, cleaning and analysis. CGX has made an important contribution to the original design of the study and data interpretation. All authors read and approved the final manuscript. Acknowledgements We would like to acknowledge the contributions of Shuli Lv whom contributed her time and efforts to the running of this study. References Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36(7):1720-48. Yamaguchi M, Suzuki R, Oguchi M. Advances in the treatment of extranodal NK/T-cell lymphoma, nasal type. Blood. 2018;131(23):2528-40. Haverkos BM, Pan Z, Gru AA, Freud AG, Rabinovitch R, Xu-Welliver M, et al. Extranodal NK/T Cell Lymphoma, Nasal Type (ENKTL-NT): An Update on Epidemiology, Clinical Presentation, and Natural History in North American and European Cases. Curr Hematol Malig Rep. 2016;11(6):514-27. Gill H, Liang RH, Tse E. Extranodal natural-killer/t-cell lymphoma, nasal type. Adv Hematol. 2010;2010:627401. Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, et al. Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood. 2009;113(17):3931-7. Kim BS, Kim TY, Kim CW, Kim JY, Heo DS, Bang YJ, et al. Therapeutic outcome of extranodal NK/T-cell lymphoma initially treated with chemotherapy--result of chemotherapy in NK/T-cell lymphoma. Acta Oncol. 2003;42(7):779-83. Li YX, Yao B, Jin J, Wang WH, Liu YP, Song YW, et al. Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma. J Clin Oncol. 2006;24(1):181-9. Lee J, Suh C, Park YH, Ko YH, Bang SM, Lee JH, et al. Extranodal natural killer T-cell lymphoma, nasal-type: a prognostic model from a retrospective multicenter study. J Clin Oncol. 2006;24(4):612-8. Liang R. Advances in the management and monitoring of extranodal NK/T-cell lymphoma, nasal type. Br J Haematol. 2009;147(1):13-21. Vose J, Armitage J, Weisenburger D, International TCLP. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124-30. Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, et al. Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211. J Clin Oncol. 2009;27(33):5594-600. Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, et al. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood. 2011;117(6):1834-9. Kim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, et al. Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell Lymphoma: Consortium for Improving Survival of Lymphoma study. J Clin Oncol. 2009;27(35):6027-32. Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, et al. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study. J Clin Oncol. 2011;29(33):4410-6. Kim SJ, Park S, Kang ES, Choi JY, Lim DH, Ko YH, et al. Induction treatment with SMILE and consolidation with autologous stem cell transplantation for newly diagnosed stage IV extranodal natural killer/T-cell lymphoma patients. Ann Hematol. 2015;94(1):71-8. Fox CP, Civallero M, Ko YH, Manni M, Skrypets T, Pileri S, et al. Survival outcomes of patients with extranodal natural-killer T-cell lymphoma: a prospective cohort study from the international T-cell Project. Lancet Haematol. 2020;7(4):e284-e94. Kim SJ, Yoon DH, Jaccard A, Chng WJ, Lim ST, Hong H, et al. A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis. Lancet Oncol. 2016;17(3):389-400. Yamaguchi M, Suzuki R, Miyazaki K, Amaki J, Takizawa J, Sekiguchi N, et al. Improved prognosis of extranodal NK/T cell lymphoma, nasal type of nasal origin but not extranasal origin. Ann Hematol. 2019;98(7):1647-55. Lee J, Au WY, Park MJ, Suzumiya J, Nakamura S, Kameoka J, et al. Autologous hematopoietic stem cell transplantation in extranodal natural killer/T cell lymphoma: a multinational, multicenter, matched controlled study. Biol Blood Marrow Transplant. 2008;14(12):1356-64. Wang H, Wang L, Li C, Wuxiao Z, Chen G, Luo W, et al. Pegaspargase Combined with Concurrent Radiotherapy for Early-Stage Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Two-Center Phase II Study. Oncologist. 2020;25(11):e1725-e31. Dong LH, Zhang LJ, Wang WJ, Lei W, Sun X, Du JW, et al. Sequential DICE combined with l-asparaginase chemotherapy followed by involved field radiation in newly diagnosed, stage IE to IIE, nasal and extranodal NK/T-cell lymphoma. Leuk Lymphoma. 2016;57(7):1600-6. Kwong YL, Kim SJ, Tse E, Oh SY, Kwak JY, Eom HS, et al. Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma. Ann Oncol. 2018;29(1):256-63. Jiang M, Zhang H, Jiang Y, Yang Q, Xie L, Liu W, et al. Phase 2 trial of "sandwich" L-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma. Cancer. 2012;118(13):3294-301. Zhang L, Jiang M, Xie L, Zhang H, Jiang Y, Yang QP, et al. Five-year analysis from phase 2 trial of "sandwich" chemoradiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma. Cancer Med. 2016;5(1):33-40. Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, et al. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012;120(15):2973-80. Gao Y, Huang H-q, QiChun C, Wang X, Cai Q, Xia Z, et al. Efficacy and Safety Of Pegaspargase With Gemcitabine and Oxaliplatin In Patients With Treatment-naïve, Refractory Extranodal Natural Killer/T-Cell Lymphoma: A Single-Centre Experience. Blood. 2013;122(21):642-. Ji J, Xiang B, Liu ZG, Jia YQ, Zhu HL, Niu T, et al. Efficacy of GLIDE chemotherapy for patients with newly diagnosed advanced-stage or relapsed/refractory extranodal natural killer cell lymphoma. Chin J Hematol. 2016;37(9):5. Ji J, Liu T, Xiang B, Liu W, He C, Chen X, et al. A study of gemcitabine, l-asparaginase, ifosfamide, dexamethasone and etoposide chemotherapy for newly diagnosed stage IV, relapsed or refractory extranodal natural killer/T-cell lymphoma, nasal type. Leuk Lymphoma. 2014;55(12):2955-7. Shen Z, Chen X, Sun C, Lu T, Shi Y, Zhang H, Ye J, Wang L, Zhu T, Miao Y, Zhang X, Wang L, Cai G, Sang W. Comparative analysis of clinicopathologic characteristics and prognosis between nasal and nonnasal extranodal NK/T-cell lymphoma. Cancer Med. 2023 Dec;12(23):21138-21147. Montes-Mojarro IA, Chen BJ, Ramirez-Ibarguen AF, Quezada-Fiallos CM, Pérez-Báez WB, Dueñas D, Casavilca-Zambrano S, Ortiz-Mayor M, Rojas-Bilbao E, García-Rivello H, Metrebian MF, Narbaitz M, Barrionuevo C, Lome-Maldonado C, Bonzheim I, Fend F, Steinhilber J, Quintanilla-Martinez L. Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America. Mod Pathol. 2020 May;33(5):781-791. Shen Z, Zhang S, Chen X, Zhang Q, Jiao Y, Shi Y, Zhang H, Ye J, Wang L, Zhu T, Miao Y, Wang L, Cai G, Sang W. Prognostic value of prognostic nutritional index on extranodal natural killer/T-cell lymphoma patients: A multicenter propensity score matched analysis of 1022 cases in Huaihai Lymphoma Working Group. Hematol Oncol. 2023 Aug;41(3):380-388. doi: 10.1002/hon.3124. Epub 2023 Jan 29. PMID: 36680513. Wang C, Bai H, Xi R, Pan Y, Xu S, Zhang Q, Chen Y, Zhou J. [Curative effect of nasal type extranodal NK/T-cell lymphoma by sequential chemotherapy combined radiotherapy compared with chemotherapy]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2013 Dec;27(23):1283-6, 1290. Yang CW, Wang CW, Hong RL, Tsai CL, Yao M, Tang JL, Lin CW, Cheng AL, Kuo SH. Treatment outcomes of and prognostic factors for definitive radiotherapy with and without chemotherapy for Stage I/II nasal extranodal NK/T-cell lymphoma. J Radiat Res. 2017 Jan;58(1):114-122. Yan Z, Yao S, Wang Z, Zhou W, Yao Z, Liu Y. Treatment of extranodal NK/T-cell lymphoma: From past to future. Front Immunol. 2023 Feb 7;14:1088685. Wei YC, Qi F, Zheng BM, Zhang CG, Xie Y, Chen B, Liu WX, Liu WP, Fang H, Qi SN, Zhang D, Chai Y, Li YX, Wang WH, Song YQ, Zhu J, Dong M. Intensive therapy can improve long-term survival in newly diagnosed, advanced-stage extranodal NK/T-cell lymphoma: A multi-institutional, real-world study. Int J Cancer. 2023 Nov 1;153(9):1643-1657. Chauchet A, Michallet AS, Berger F, Bedgedjian I, Deconinck E, Sebban C, Antal D, Orfeuvre H, Corront B, Petrella T, Hacini M, Bouteloup M, Salles G, Coiffier B. Complete remission after first-line radio-chemotherapy as predictor of survival in extranodal NK/T cell lymphoma. J Hematol Oncol. 2012 Jun 8;5:27. Tables Table 1 Clinical characteristics and treatment details of 408 ENKTL patients (n=408) Total Nasal-type Extranasal- type χ ² P Age 1.586 0.208 ≤60 years 354 (86.8) 298 (85.9) 56 (91.8) >60 years 54 (13.2) 49 (14.1) 5 (8.2) Gender 0.652 0.420 Male 266 (65.2) 229 (66.0) 37 (60.7) Female 142 (34.8) 118 (34.0) 24 (39.3) B symptoms 2.423 0.120 No 198 (48.5) 174 (50.1) 24 (39.3) Yes 210 (51.5) 173 (49.9) 37 (60.7) ECOG 51.195 ＜0.001 <2 372 (91.2) 331 (95.4) 41 (67.2) ≥2 36 (8.8) 16 (4.6) 20 (32.8) LDH 42.488 ＜0.001 ＜250 279(68.4) 259(74.6) 20(32.8) 250-499 103(25.2) 74(21.3) 29(47.5) 500-749 15(3.7) 9(2.6) 6(9.8) ≥750 11(2.7) 5(1.4) 6(9.8) Ann Arbor stage 98.175 ＜0.001 Ⅰ-Ⅱ 290 (71.1) 279 (80.4) 11 (18.0) Ⅲ-Ⅳ 118 (28.9) 68 (19.6) 50 (82.0) PINK-E score 73.529 ＜0.001 0 75 (18.4) 75 (21.6) 0 (0.0) 1 188 (46.1) 178 (51.3) 10 (16.4) ≥2 145 (35.5) 94 (27.1) 51 (83.6) Bone marrow involvement 5.322 0.021 No 400 (98.0) 343 (98.8) 57 (93.4) Yes 8 (2.0) 4 (1.2) 4 (6.6) Distant lymph node involvement 32.788 ＜0.001 No 358 (87.7) 318 (91.6) 40 (65.6) Yes 50 (12.3) 29 (8.4) 21 (34.4) First-line treatment 94.719 ＜0.001 Radiotherapy alone 11(2.7) 11(3.2) 0(0.0) Chemotherapy alone 93(22.8) 57(16.4) 3(59.0) Chemotherapy and radiotherapy 280(68.6) 269(77.5) 11(18.0) Chemotherapy and ASCT 24(5.9) 10(2.9) 14(23.0) First-line treatment achieved CR 8.748 0.003 No 158(38.7) 124(35.7) 34(55.7) Yes 250(61.3) 223(64.3) 27(44.3) Chemotherapy regimen 24.840 ＜0.001 L-asparaginase+, platinum+, gemcitabine- 201(49.3) 184(53.0) 17(27.9) L-asparaginase+, platinum-, gemcitabine+ 102(25.0) 74(21.3) 28(45.9) L-asparaginase+, platinum+, gemcitabine+ 64(15.7) 54(15.6) 10(16.4) L-asparaginase+, platinum-, gemcitabine- 11(2.7) 7(2.0) 4(6.6) L-asparaginase-, platinum+, gemcitabine+ 8(2.0) 7(2.0) 1(1.6) L-asparaginase-, platinum+, gemcitabine- 6(1.5) 6(1.7) 0(0.0) L-asparaginase-, platinum-, gemcitabine- 4(1.0) 3(0.9) 1(1.6) ENKTL=extranodal natural killer T-cell lymphoma.ECOG=Eastern Cooperative Oncology Group. ASCT= autologous hematopoietic stem cell transplantation.LDH= lactate dehydrogenase. PINK= the prognostic index of natural killer Lymphoma Table 2 Univariate and multivariate analysis of overall survival in 408 patients with ENKTL Univariate analysis Multivariate analysis HR (95%CI) P HR (95%CI) P Age (>60 years /≤60 years) 1.394(0.810-2.400) 0.231 Gender (female / male) 0.897(0.573-1.402) 0.633 Nasal-type (yes/no) 0.313(0.194-0.505) ＜0.001 B symptoms (yes/no) 2.769(1.738-4.414) ＜0.001 ECOG (≥2/<2) 6.268(3.784-10.384) ＜0.001 2.728(1.563-4.761) ＜0.001 LDH (＜250) 250-499 2.991(1.905-4.694) ＜0.001 500-749 3.179(1.256-8.050) 0.015 ≥750 4.172(1.494-11.653) 0.006 Ann Arbor stage (Ⅲ-Ⅳ/Ⅰ-Ⅱ) 3.796(2.482-5.804) ＜0.001 PINK-E score (0) 1 1.585(0.724-3.470) 0.249 ≥2 4.855(2.295-10.270) ＜0.001 Bone marrow involvement (yes/no) 3.603(1.319-9.840) 0.012 Distant lymph node involvement (yes/no) 2.414(1.399-4.165) 0.002 First-line treatment (Chemotherapy alone) Radiotherapy alone 11.107(1.525-80.923) 0.017 0.146(0.020-1.088) 0.060 Chemotherapy and radiotherapy 1.697(0.233-12.361) 0.602 0.303(0.184-0.501) <0.001 Chemotherapy and ASCT 3.731(0.459-30.332) 0.218 0.373(0.162-0.857) 0.020 First-line treatment achieved CR 0.412(0.269-0.631) <0.001 0.565(0.364-0.877) 0.011 HR: Hazard ratio. 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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-5768765","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":398306950,"identity":"7d826c3a-d567-44a3-b4b7-8422763c64f1","order_by":0,"name":"Jie Wang","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Wang","suffix":""},{"id":398306951,"identity":"4b26ffc8-f179-48ea-af3d-ceb2a645eb54","order_by":1,"name":"Yunfan Yang","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Yunfan","middleName":"","lastName":"Yang","suffix":""},{"id":398306952,"identity":"ecb2444b-1a42-4067-9658-53c0ab8a43e1","order_by":2,"name":"Chunlan Zhang","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Chunlan","middleName":"","lastName":"Zhang","suffix":""},{"id":398306953,"identity":"603f9034-9a90-4a06-ad38-c925833952d3","order_by":3,"name":"Xushu Zhong","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Xushu","middleName":"","lastName":"Zhong","suffix":""},{"id":398306954,"identity":"9ebf0549-80a4-4f11-8b73-84b70badb49c","order_by":4,"name":"Qinyu Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYBAC+4aDjY9//qnh4WdvIFKLAePhZmPGhmNykj0HiNXCfLxNmLGB2djgRgKRWszZDrYxF+5gS2y4+XjjDYYam2iCWix7DrY9nnlGJrFxdlqxBcOxtNwGgnpuHGw34GFjS2yWzjGTYGw4TISW+w/bJHjYmBPbJM8QqcXgwME2ad42ZmMeCR4itUg2HGw2nHHmmJwED9AvCcT4hZ/h+MMHHypqeOyPH95440ONDRF+QXakRAIpyiFaSNUxCkbBKBgFIwMAAIHHRWCJQMXlAAAAAElFTkSuQmCC","orcid":"","institution":"Sichuan University","correspondingAuthor":true,"prefix":"","firstName":"Qinyu","middleName":"","lastName":"Liu","suffix":""},{"id":398306955,"identity":"bc10f93a-1dc8-483f-b976-d3f2f27303d7","order_by":5,"name":"Caigang Xu","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Caigang","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2025-01-05 16:38:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5768765/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5768765/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73339329,"identity":"35e9f675-1cc0-4ad2-8648-23802f57d290","added_by":"auto","created_at":"2025-01-09 05:07:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1821492,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analyses in all patients and by ENKTL subtype. Overall survival (A) and progression-free survival (B) of all ENKTL patients; overall survival (C) and progression-free survival (D) by ENKTL nasal type (n = 347) or extranasal type (n = 61).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5768765/v1/4032957758a43441ed0c9c71.png"},{"id":73337981,"identity":"eb0cdd18-38a0-4781-adc2-f59352b44cf5","added_by":"auto","created_at":"2025-01-09 04:51:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":514444,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analyses by disease stage and PINK-E score. Overall survival (A) and progression-free survival (B) of stage I ~ II and stage III ~ IV; OS (C) and PFS (D) of different PINK-E groups.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5768765/v1/d02a3249c80dfc4c11a0fca7.png"},{"id":73337989,"identity":"3916135d-344b-4b32-8a7e-203bce1a314f","added_by":"auto","created_at":"2025-01-09 04:51:17","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3881899,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analyses in early-stage and advanced-stage patients according to first-line treatment. OS (A) and PFS (B) of early-stage (stage I and II) patients treated with chemotherapy alone (n = 27) or chemotherapy and radiotherapy (n = 249) according to the first-line treatment; OS (C) and PFS (D) for advanced-stage (stage III and IV) patients treated with chemotherapy alone (n = 66), chemotherapy and radiotherapy (n = 31), chemotherapy and ASCT (n = 21) as first-line therapy.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5768765/v1/f922c2aad92621ac26a2f0f0.png"},{"id":73337988,"identity":"e3832caa-ef59-4f93-b76c-5000989df2c1","added_by":"auto","created_at":"2025-01-09 04:51:17","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":405712,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analyses in early-stage and advanced-stage patients according to with or without asparaginase-based regimens. OS (A) and PFS (B) of patients on early stage (stage I and II) with asparaginase-based regimens (n = 264) and patients without asparaginase-based regimens (n = 14); 0S (C) and PFS (D) of patients on advanced stage (stage III and IV) with asparaginase-based regimens (n = 114) and asparaginase-free regimens (n = 4).\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5768765/v1/192808b3f10082217f510cce.png"},{"id":73339044,"identity":"240a7671-61fb-4fbe-9bf7-c68235e2a68d","added_by":"auto","created_at":"2025-01-09 04:59:17","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1149551,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment response to asparaginase-based chemotherapy in advanced-stage (stage III and IV) patients.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-5768765/v1/999d14895ac82525b995fd5e.png"},{"id":73337992,"identity":"a0b69f65-17c8-475a-b8e5-8de82d9b1f87","added_by":"auto","created_at":"2025-01-09 04:51:17","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1283322,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analyses in early-stage and advanced-stage patients according to efficacy after first-line treatment. OS (A) and PFS (B) of ENKTL patients with or without CR after first-line treatment.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-5768765/v1/3e89a6b153cd4c7c12c081ec.png"},{"id":73337996,"identity":"c60de4eb-97cb-474d-ac94-d0009370b4ce","added_by":"auto","created_at":"2025-01-09 04:51:17","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":2412699,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analyses in nasal and extranasal patients according to efficacy after first-line treatment. OS (A) and PFS (B) of nasal (n = 223) and extranasal (n = 27) patients with CR after first-line treatment; OS (C) and PFS (D) of nasal type (n = 124) and extranasal type (n = 34) of patients who did not achieve CR after first-line treatment.\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-5768765/v1/82b27f4e221b6ccf58e3fc17.png"},{"id":73653972,"identity":"51cd3e06-eab3-4691-a701-4fd6287c841a","added_by":"auto","created_at":"2025-01-13 10:02:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":11051601,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5768765/v1/9c9e162a-e8d5-4c5e-976c-6a909bc2e541.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-term survival of extranodal NK/T-cell lymphoma: a single-center real- world study of 408 cases in China","fulltext":[{"header":"Introduction","content":"\u003cp\u003eExtranodal NK/T-cell lymphoma (ENKTL) is a rare aggressive lymphoma, which was formally included in the WHO classification of hematopoietic and lymphoid tumors in 1999 and updated in 2022 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This disease exhibits a distinct geographical distribution, with a lower prevalence in Europe and North America compared to a higher incidence in East Asia and Central and South America [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The exact etiology of ENKTL remains unclear, but it is strongly associated with Epstein-Barr (EB) virus infection, a factor that is not geographically confined [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eClinically, ENKTL is characterized by its aggressive nature and resistance to conventional anthracycline-based chemotherapy [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], leading to a generally poor prognosis. Radiation therapy has emerged as a critical component in the management of localized ENKTL, offering significant benefits in controlling localized lesions [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, extranasal involvement and advanced disease stages are major prognostic factors associated with poorer outcomes [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Data from a previous international peripheral T-cell lymphoma project [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] revealed that the median progression-free survival for the entire ENKTL cohort was only 6 months, with an overall survival of just 8 months, making it the subtype with the worst survival outcomes among all T-cell lymphomas [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Notably, the majority of these cases were nasal in origin.\u003c/p\u003e \u003cp\u003eIn recent years, the therapeutic landscape for ENKTL has evolved, with growing evidence supporting the use of concurrent or sequential radiotherapy combined with anthracycline-free chemotherapy for localized lesions [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. For advanced-stage and relapsed or refractory ENKTL, non-anthracycline-based chemotherapy regimens, particularly those incorporating L-asparaginase, have shown promise [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A recent international study reported a 5-year overall survival rate of 54% for nasal-type ENKTL and 34% for extranasal-type ENKTL [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aims to evaluate the prognosis and treatment outcomes of patients with ENKTL through an examination of their clinical characteristics and survival data. Specifically, the study focuses on the impact of various treatment strategies on clinical outcomes in the pre-new drug era.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and patients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study originated from an international multicenter, hospital-based case-control study of lymphoma in Asia, which was initiated in 2012.Within this broader project, this retrospective real-world study enrolled patients with ENKTL at West China Hospital Affiliated to Sichuan University between January, 2012 and December, 2017. Patient enrollment conditions were based on local histologic diagnosis. Inclusion criteria: 1) Patients must be 18 years of age or older. 2) Adequate tissue biopsies must be available for diagnosis and classification. 3) Comprehensive clinical data, including baseline information on disease stage and laboratory ancillary tests at diagnosis, must be available. 4) Detailed records of the type of treatment received must be documented. 5) Patients must have at least 5 years of follow-up data. Those with incomplete data were excluded. The study was approved by the Ethics Committee on Biomedical Research of our hospital, and all patients provided written informed consent prior to study entry.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and definitions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe first ENKTL patient was enrolled in the program on January 28, 2012, and the last patient was enrolled on December 29, 2017. According to the World Health Organization (WHO) 2008 classification, previously untreated ENKTL patients at our hospital were enrolled to receive any treatment. The treatment strategy involves radiotherapy, chemotherapy and autologous hematopoietic stem cell transplantation. As this was a retrospective study, there were many specific chemotherapy schemes. The chemotherapy schemes were divided into two categories, including with/without asparaginase. Further subdivided into 7 types, including L-asparaginase+, platinum+, gemcitabine-; L-asparaginase+, platinum-, gemcitabine+; L-asparaginase+, platinum+, gemcitabine+; L-asparaginase+, platinum-, gemcitabine-; L-asparaginase-, platinum+, gemcitabine+; L-asparaginase-, platinum+, gemcitabine-; and L-asparaginase-, platinum-, gemcitabine-.\u003c/p\u003e\n\u003cp\u003eData were collected on baseline clinical and disease characteristics, Eastern Cooperative Oncology Group (ECOG) performance status, first-line treatment and response assessment, and updated survival follow-up. Additionally, we analyzed the ENKTL cohort using the PINK-E index. This index incorporates EBV-DNA positivity into the Prognostic Index of Natural Killer Lymphoma (PINK) score, first published in 2016, and includes five risk factors: age \u0026gt;60 years, stage III or IV, distant lymph node involvement, extranasal lesions, and EBV-DNA positivity [17]. According to the prognostic index, patients were categorized into three groups: low-risk (0-1 risk factors), intermediate-risk (2 risk factors), and high-risk (\u0026ge;3 risk factors).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was 5-year overall survival (OS), and the secondary outcome was 5-year progression-free survival (PFS). Other predefined endpoints included the proportion of patients who achieved remission after initial treatment. OS was defined as the time from diagnosis to death from any cause, or the date of the last known contact for living patients. PFS was defined as the time from diagnosis to disease progression or death due to lymphoma.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using SPSS Statistics for Windows, Version 19.0 (Armonk, NY: IBM Corp.) and R software (version 4. 0.3; http://www. R-project. org). Categorical variables were presented as numbers (percentages). Differences in categorical variables were analyzed using the \u0026chi;\u0026sup2; test. Continuous variables were dichotomized using MaxStat analysis (Maximally Selected Rank Statistics). The Cox proportional hazards model was used to analyze the univariable association between prognostic factors and overall survival (OS). All variables with P \u0026lt; 0.05 in the univariable analysis were included in the multivariable analysis. Forward selection was used to identify the best predictor set, and the Akaike Information Criterion (AIC) was employed to evaluate the model fit. Kaplan-Meier analysis was used to estimate survival outcomes, and the log-rank test was performed to compare differences between groups. All statistical tests were two-sided, and statistical significance was set at P \u0026lt; 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAs of the data cut-off date (January 1, 2018), 408 patients were enrolled for analysis. Of these cases, 347 (85%) were defined as nasal and 61 (15%) were defined as extranasal type. \u003cstrong\u003eTable 1\u003c/strong\u003e shows the baseline clinical characteristics of the patients. As expected, patients with extranasal type showed more adverse clinical features than nasal type, especially in ECOG\u0026nbsp;performance status, lactate dehydrogenase (LDH), stage III-IV, PINK-E score, bone marrow involvement, and distant lymph node involvement (all P \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003eAt a median OS follow-up of 56.0 months (95% CI 51.8-60.2), all ENKTL patients (n=408) had a 3-year OS of 79.2% and a 5-year OS of 75.3% (\u003cstrong\u003eFigure 1A\u003c/strong\u003e). In patients with nasal type, the 5-year OS was 78.8 %, which was significantly higher than that in patients with extranasal type (45.1%), and the difference was statistically significant (P \u0026lt; 0.001) (\u003cstrong\u003eFigure 1C\u003c/strong\u003e). At a median PFS follow-up of 55. 0 months (95 % CI 50.8-59.2), the 3-year PFS of all ENKTL patients was 77.8 %, and the 5-year PFS was also 75.3% (\u003cstrong\u003eFigure 1B\u003c/strong\u003e). The 5-year PFS of patients with nasal type was 78. 8%, which was significantly higher than that of patients with extranasal type (45.6 %) (P \u0026lt; 0.001) (\u003cstrong\u003eFigure 1D\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eAccording to the Ann Arbor stage, the 5-year OS and 5-year PFS of patients with early stage (stage I and II) were 83.0 % and 90.9 %, respectively, while the 5-year OS and 5-year PFS of patients with advanced stage (stage III and IV) were 53.5 % and 73.5 %, respectively, both with statistically significant differences (P \u0026lt; 0.001) (\u003cstrong\u003eFigure 2A\u003c/strong\u003e and \u003cstrong\u003eB\u003c/strong\u003e). From the available data, the PINK-E score could be calculated for 408 cases. Among them, 75 cases (18.4 %) were classified as low-risk group, 188 cases (46.1 %) as medium-risk group, and 145 cases (35.5 %)\u0026nbsp;as high-risk group. The 5-year OS was 89. 6% in the low-risk group, 81.2% in the intermediate-risk group, and 57.8% in the high-risk group (P \u0026lt; 0.001; \u003cstrong\u003eFigure 2C\u003c/strong\u003e). The 5-year PFS was 89.7% in the low-risk group, 81. 1% in the intermediate-risk group, and 57.8 % in the high-risk group, with statistically significant differences (P \u0026lt; 0.001; \u003cstrong\u003eFigure 2D\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eOf the 408 patients analyzed, 280 (68.6%) patients received chemotherapy and radiotherapy as first-line treatment and 24 (5.9%) patients received chemotherapy and ASCT consolidation as first-line treatment (\u003cstrong\u003eTable 1\u003c/strong\u003e). Among the regimens containing asparaginase used in 378 patients, VDLP regimen (L-asparaginase, cisplatin, dexamethasone and etoposide) was the most commonly used, implemented in 229 (60. 6%) patients and used mainly in the combination of radiotherapy and chemotherapy in patients with early ENKTL; followed by the GLIDE regimen (gemcitabine, etoposide, ifosfamide, L-asparaginase and dexamethasone), implemented in 103 (27. 4%) patients and used mainly for chemotherapy in patients with advanced ENKTL; other asparaginase-containing regimens include P-GemOx (pegaspargase, gemcitabine and oxaliplatin), DDGP (dexamethasone, cisplatin, gemcitabine and pegaspargase), AspaMetDex (L-asparaginase, methotrexate and dexamethasone), etc.\u003c/p\u003e\n\u003cp\u003eFor early-stage (stages I and II) patients receiving chemotherapy alone (n = 27), the 3-year OS was 56.7 %, the 5-year OS was 56.7 %, the 3-year PFS was 85.9 %, and the 5-year PFS was 85.9 %. In contrast, for early-stage patients (n=249) who received the combination of chemotherapy and radiotherapy, the 3-year OS was 88.6 %, the 5-year OS was 84.5 %, the 3-year PFS was 91.2 %, and the 5-year PFS was 91.2 % (\u003cstrong\u003eFigure 3A\u003c/strong\u003e and \u003cstrong\u003eB\u003c/strong\u003e), and the combination of chemotherapy and radiotherapy was significantly better than that of patients who received chemotherapy alone.\u003c/p\u003e\n\u003cp\u003eFor advanced-stage (stage III and IV) patients receiving chemotherapy alone (n = 66), 3-year OS was 41.5 %, 5-year OS was 34.7 %, 3-year PFS was 73.0%, and 5-year PFS was 73.0 %. In contrast, among patients with advanced disease who received chemotherapy and radiotherapy (n=31), 3-year OS was 85.9 %, 5-year OS was 80.2 %, 3-year PFS was 82.6 %, 5-year PFS was 82.6%; among patients who received chemotherapy and ASCT (n=21), 3-year OS was 63.3 %, 5-year OS was 63.3 %, 3-year PFS was 65.6 %, and 5-year PFS was 65.6 % (\u003cstrong\u003eFigure 3C\u003c/strong\u003e and \u003cstrong\u003eD\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eWe then explored the effects of different chemotherapy regimens on survival outcomes of ENKTL. Classified by chemotherapy regimens, all patients receiving asparaginase-based regimens had 5-year PFS of 87.0% and 5-year OS of 75.2%, while those receiving asparaginase-free regimens had 5-year PFS of 92.9% and 5-year OS of 63.8%.\u003c/p\u003e\n\u003cp\u003eFor early-stage patients, the 5-year PFS was 90. 9 % and the 5-year OS was 83. 0 % for the asparaginase-based regimen versus 91.7 % and 73.4 % for the asparaginase-free regimen (\u003cstrong\u003eFigure 4A\u003c/strong\u003e and \u003cstrong\u003eB\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eFor advanced-stage patients, the 5-year PFS of the asparaginase-based regimen was 54. 6 % and the 5-year OS was 54.7 %, while the 5-year PFS of the asparaginase-free regimen was 0.0 % and the 5-year OS was 0.0 % (\u003cstrong\u003eFigure 4C\u003c/strong\u003e and \u003cstrong\u003eD\u003c/strong\u003e), the differences were statistically significant. There were also differences in the treatment response of different chemotherapy regimens based on asparaginase (\u003cstrong\u003eFigure 5\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eOverall, 250 (61.3%) of 408 patients (including 223 nasal and 27 extranasal) achieved CR after first-line treatment, with the 5-year OS of 81.9% (85.5% nasal and 48.6% extranasal), and 5-year PFS of 82.0% (85.5% nasal and 48.9% extranasal). In contrast, patients who did not achieve CR with first-line therapy had significantly poorer outcomes, with the 5-year OS of 63.2% and 5-year PFS of 63.0% (\u003cstrong\u003eFigure 6\u003c/strong\u003e and \u003cstrong\u003eFigure 7\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eThe effects of various factors on the survival of patients were analyzed. The results of univariate analysis of Cox regression model showed that nasal type, ECOG, LDH, B symptoms, Ann Arbor stage, PINK-E score, bone marrow involvement, distant lymph node involvement, first-line treatment, whether first-line treatment achieved CR were risk factors for patient prognosis, with statistically significant differences (P \u0026lt; 0.05). Multivariate analysis showed that ECOG (HR=2.728, 95%CI: 1.563-4.761, P \u0026lt; 0.001); type of first-line treatment, including chemotherapy and radiotherapy (HR=0.303, 95%CI: 0.184-0.501, P \u0026lt; 0.001), chemotherapy and ASCT (HR=0.373, 95%CI: 0.162-0.857, P = 0.020), and first-line treatment achieved CR (HR=0.565, 95%CI: 0.364-0.877, P = 0.011), were independent prognostic factors for patients\u0026rsquo; OS (\u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that different treatment strategies might impact the long-term survival of patients with ENKTL before the era of new drugs. Chemotherapy combined with radiotherapy, asparaginase-based regimens, and achieving complete remission (CR) after first-line treatment are associated with improved outcomes, particularly in early-stage and advanced-stage patients. Moreover, ECOG performance status, type of first-line treatment were independent prognostic factors for OS. These findings highlight the importance of tailored treatment approaches in managing ENKTL.\u003c/p\u003e\n\u003cp\u003eTo our knowledge, this paper presents the largest study to date of patients with ENKTL before the era of new drugs. A total of 408 patients with NK/T-cell lymphoma were enrolled in the lymphoma project launched in 2012. Compared to the International Peripheral T-cell Lymphoma Program reported in 2009 (including 136 patients with ENKTL from 1990 to 2002 from 22 centers in 13 countries) [5]. We found that the survival rate of ENKTL patients was significantly improved, representing the largest change in clinical outcomes among all T-cell lymphoma subtypes studied in the past decade. This improvement may be attributed to the evolution of clinical regimens, including a shift from anthracycline-based therapy to asparaginase-based and platinum-based regimens and the increasing use of radiotherapy. In this study, the improvement of survival rate was significantly correlated with ECOG score, EBV-DNA quantification, baseline Hb and PLT, and CR in first-line treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the entire ENKTL cohort, we observed a similar proportion of extranasal cases (61 cases in 15%) as previously reported in population-based studies. As expected, survival rates were significantly lower in patients with extranasal type than in patients with nasal type. Consistent with this result, advanced-stage (stage III and IV) patients had a significantly worse prognosis than early-stage (stage I and II) patients.\u003c/p\u003e\n\u003cp\u003eAlthough the prognostic prediction of ENKTL is not straightforward, distinguishing between early and advanced stage is crucial for treatment a planning and prognosis [18]. In 2016, the ENKTL-specific prognostic index PINK was described, and the score showed a better prognostic description in the context of non-anthracycline therapy [17]. This score was further refined in advanced disease to include detectable Epstein-Barr virus DNA in peripheral blood as an additional parameter (PINK-E) [17]. We validated the PINK-E score in the ENKTL cohort and confirmed that a high-risk PINK score can identify patients with a particularly poor prognosis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProspective studies of rare malignancies like NK/T-cell lymphoma are essential to improve understanding of the epidemiological and clinical factors affecting the course of the disease and to provide information on treatment patterns and survival outcomes. Our ENKTL dataset has both strengths and limitations as a single-center study. The study centrally registers data from patients with ENKTL diagnosed over 6 consecutive years at the largest single-center size hospital in China, allowing insight into the clinical features of ENKTL and providing measures of its modern clinical treatment. Moreover, the long-term follow-up of the study made the data on survival outcomes trustworthy. However, the size and scope of single-center data is also somewhat restrictive.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProfessor Au [5] reported in 2009 an international peripheral T-cell lymphoma retrospective project in which 136 (11.8%) of 1153 newly diagnosed peripheral T-cell lymphoma adult cases from 1990-2002 in 22 centers in 13 countries were ENKTL (68% nasal, 26% extranasal and 6% unclassifiable). The statistical prevalence was higher in Asian countries than in Western countries (22% and 5%) and higher in mainland Asia than in Japan (34%-56% and 11%). As expected, the survival outcome of extranasal type was significantly worse than that of nasal type, and consistent with this result, prognosis was significantly worse in advanced stage than in early stage. The median OS and PFS of the entire cohort were only 0.65 years and 0.48 years (7.8 and 5.8 months), respectively, which was the worst survival rate of all PTCLs in the project. Except for those with early-stage nasal diseases, survival rates of more than 1 year are not common. Recently, a study of the International T-cell Lymphoma Project showed [16] that 166 patients were diagnosed with ENKTL and during the median follow-up of 44 months, the 5-year overall survival rate of nasal patients (n = 98) was 54 %, and that of extranasal patients (n = 68) was 34 %.\u003c/p\u003e\n\u003cp\u003eThe 5-year overall survival rate was 55% for stage I patients, 42% for stage II patients, and 24 % for stage III~IV patients. In our study, the 5-year overall survival was 78.8 % in patients with nasal type and 45.1 % in patients with extranasal type. The 5-year OS of patients with stage I and II was 83. 0 %, and that of patients with stage III and IV was 53.5 %. The significant improvement in PFS and OS represents a paradigm shift in the clinical management of patients with ENKTL.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe principles of treatment for early and advanced disease in ENKTL differ, with early stages being treated with a combination of radiotherapy and chemotherapy, while advanced stages are dominated by chemotherapy, with residual lesions being considered for local and radiotherapy, and patients with advanced disease who achieve high-quality remission may benefit from autologous transplantation [19]. In the past decade, significant differences in treatment modalities include a significant decline in the proportion of patients receiving anthracyclines, and a corresponding increase in the proportion of patients receiving platinum or asparaginase. Prospective clinical studies have shown the important prognostic value of asparaginase in ENKTL treatment regimens [12, 14], and radiotherapy combined with asparaginase chemotherapy has become the cornerstone of initial treatment for patients with early-stage ENKTL [20]. Our study emphasizes the important role of radiotherapy in the treatment of ENKTL. In patients with early disease, the combination of chemotherapy and radiotherapy was associated with improved survival (5-year survival rate was 845 %), and chemotherapy alone was associated with poor prognosis (5-year survival rate was 56.7 %). The sequence of radiotherapy and chemotherapy in ENKTL includes sequential chemoradiotherapy, concurrent chemoradiotherapy and \u0026apos; sandwich \u0026apos; therapy. Currently, chemotherapy sequential radiotherapy is a common mode. In previous studies, the 5-year PFS and OS rates of early-stage ENKTL patients receiving sequential radiotherapy chemoradiotherapy were 64%~83% and 64%~89%, respectively, and most of them were treated with chemotherapy followed by radiotherapy [21]. Concurrent radiotherapy is common in Japan and Korea, but rare in other countries, and some studies suggest that concurrent radiotherapy is equivalent to sequential radiotherapy [22]. \u0026apos;Sandwich \u0026apos; therapy refers to radiotherapy after 2~3 cycles of chemotherapy (50~56 Gy, 25~28 times a day, 5 times a week), followed by 2~3 consolidation cycles of chemotherapy. Professor Zou Liqun \u0026apos;s team at our hospital reported that the \u0026apos; sandwich \u0026apos; therapy achieved an CR rate of 80. 8%~83. 3% for early stage ENKTL, with both 5-year PFS and OS rates of 64 % [ 23,24 ]. However, the potential impact of different chemotherapy regimens on radiotherapy efficacy and dose requirements is still not well defined.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor advanced-stage patients, asparaginase-containing chemotherapy is the most effective systemic chemotherapy. The SMILE [20, 25] and AspaMetDex regimens recommended by the NCCN guidelines are highly effective [12], but the toxicity is also obvious. The P-GemOx regimen is a simple and cost-effective option with manageable toxicities [26]. Dr. Ji Jie from our hospital previously reported that the GLIDE regimen (gemcitabine, asparaginase, ifosfamide, dexamethasone, and etoposide) was used to treat 42 patients with newly diagnosed advanced and relapsed refractory ENKTL, and 31 patients (73.8 %) achieved CR, of whom 14 patients received sequential ASCT, with 1-year PFS and OS rates of 656% and 827%, respectively, and 4-year PFS and OS rates were 48. 2% and 63. 1%, respectively [27, 28]. In this study, the chemotherapy regimens containing asparaginase were divided into the following 7 categories: (i) asparaginase+, platinum+, gemcitabine- (advanced-stage, mainly VDLP regimen); (ii) asparaginase+, platinum-, gemcitabine+ (advanced-stage, mainly GLIDE regimen); (iii) asparaginase+, platinum+, gemcitabine+ (advanced-stage, mainly DDGP); (iv) asparaginase+, platinum-, gemcitabine- (advanced-stage, mainly AspaMetDex regimen); (v)\u0026nbsp;L-asparaginase-, platinum+, gemcitabine+; (vi) L-asparaginase-, platinum+, gemcitabine-; (vii) L-asparaginase-, platinum-, gemcitabine-. Among them, the second category of chemotherapy regimen containing asparaginase and gemcitabine as the first-line treatment had the highest CR rate of 40 % in advanced-stage ENKTL, followed by the first category of chemotherapy regimen containing asparaginase and platinum (CR rate was 28.6 %).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMoreover, multivariate analysis identified several independent prognostic factors for overall survival (OS) in patients with extranodal NK/T-cell lymphoma (ENKTL). Specifically, ECOG performance status was a significant predictor of worse outcomes, consistent with findings from previous studies [29, 30]. Poor performance status often reflects a higher tumor burden and systemic involvement, which can negatively impact treatment tolerance and efficacy [31]. The type of first-line treatment was also a critical factor. Patients receiving chemotherapy combined with radiotherapy and chemotherapy followed by autologous stem cell transplantation (ASCT) had significantly better OS. This finding aligns with the current consensus that multimodal therapy, particularly the combination of chemotherapy and radiotherapy, is essential for optimal outcomes in ENKTL [32, 33]. Radiotherapy is particularly effective in controlling localized disease, while chemotherapy addresses systemic disease and reduces the risk of distant metastasis [34]. Achieving complete remission (CR) after first-line treatment was another independent prognostic factor. This is consistent with the literature, which emphasizes the importance of achieving CR in improving long-term survival in lymphomas [35, 36]. Early and complete eradication of the disease can prevent the development of resistant clones and reduce the likelihood of relapse. These findings underscore the importance of a comprehensive and individualized approach to treating ENKTL. Tailoring treatment strategies based on patient characteristics and disease stage can significantly improve outcomes. Future research should focus on optimizing treatment protocols and identifying biomarkers to further personalize therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths and Limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study utilizes real-world data from a substantial cohort of 408 patients, providing valuable insights into the clinical practices and outcomes associated with the treatment of extranodal natural killer/T-cell lymphoma (ENKTL) in a practical setting. It encompasses a comprehensive analysis of various treatment strategies, clinical characteristics, and survival outcomes, thereby facilitating a thorough understanding of the factors influencing patient prognosis. The application of multivariate Cox proportional hazards regression analysis allowed for the identification of independent prognostic factors, yielding robust and reliable findings. With a median follow-up of 56.0 months for overall survival (OS) and 55.0 months for progression-free survival (PFS), the study presents long-term survival data that are critical for evaluating the effectiveness of different treatment strategies. Furthermore, subgroup analyses based on disease stage, type of first-line treatment, and PINK-E score provide a nuanced understanding of how these factors impact patient outcomes.\u003c/p\u003e\n\u003cp\u003eNevertheless, this study is subject to certain limitations. First, it was conducted at a single center, which may limit the generalizability of the findings to other populations or regions characterized by differing clinical practices and patient demographics. Second, the study is situated in the pre-new drug era, suggesting that the results may not be directly applicable to the contemporary treatment landscape, which now includes newer agents and therapies. Third, despite the implementation of multivariate analysis, there may still exist unmeasured confounding factors that could affect the results. Finally, variability in treatment regimens and dosing among different patients may influence the comparability of the outcomes, although efforts were made to standardize treatment protocols to the greatest extent possible. Despite these limitations, this study offers significant insights into the long-term survival and treatment outcomes of ENKTL, underscoring the necessity for tailored and multidisciplinary approaches in the management of this aggressive lymphoma.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study demonstrated that various treatment strategies might have significantly influence on the long-term survival of patients with ENKTL prior to the introduction of novel pharmacological agents. The combination of chemotherapy and radiotherapy, asparaginase-based regimens, and the achievement of CR following first-line treatment were associated with improved outcomes, particularly among both early-stage and advanced-stage patients. Furthermore, the ECOG performance status and the nature of the first-line treatment emerged as independent prognostic factors for OS. These findings underscore the importance of personalized treatment approaches in the management of ENKTL.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eENKTL: extranodal NK/T-cell lymphoma;\u003c/p\u003e\n\u003cp\u003eOS:\u0026nbsp;overall survival;\u003c/p\u003e\n\u003cp\u003ePFS:\u0026nbsp;progression-free survival;\u003c/p\u003e\n\u003cp\u003eCR:\u0026nbsp;complete remission;\u003c/p\u003e\n\u003cp\u003eECOG: Eastern Cooperative Oncology Group;\u003c/p\u003e\n\u003cp\u003eWHO: World Health Organization;\u003c/p\u003e\n\u003cp\u003ePINK: Prognostic Index of Natural Killer Lymphoma;\u003c/p\u003e\n\u003cp\u003eAIC: Akaike Information Criterion;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee on Biomedical Research of our hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients provided written informed consent prior to study entry.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSichuan Science and Technology Department for Key Research and Development projects (2019YFS0027)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJW conceived the study and played the primary role in data analysis, as well as the drafting of the manuscript and. YFY, CLZ, XSZ, JX, WJT and QYL have made a substantial contribution to the data collation, cleaning and analysis. CGX has made an important contribution to the original design of the study and data interpretation. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge the contributions of Shuli Lv whom contributed her time and efforts to the running of this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36(7):1720-48. \u003c/li\u003e\n\u003cli\u003eYamaguchi M, Suzuki R, Oguchi M. Advances in the treatment of extranodal NK/T-cell lymphoma, nasal type. Blood. 2018;131(23):2528-40. \u003c/li\u003e\n\u003cli\u003eHaverkos BM, Pan Z, Gru AA, Freud AG, Rabinovitch R, Xu-Welliver M, et al. Extranodal NK/T Cell Lymphoma, Nasal Type (ENKTL-NT): An Update on Epidemiology, Clinical Presentation, and Natural History in North American and European Cases. Curr Hematol Malig Rep. 2016;11(6):514-27. \u003c/li\u003e\n\u003cli\u003eGill H, Liang RH, Tse E. Extranodal natural-killer/t-cell lymphoma, nasal type. Adv Hematol. 2010;2010:627401. \u003c/li\u003e\n\u003cli\u003eAu WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, et al. Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood. 2009;113(17):3931-7. \u003c/li\u003e\n\u003cli\u003eKim BS, Kim TY, Kim CW, Kim JY, Heo DS, Bang YJ, et al. Therapeutic outcome of extranodal NK/T-cell lymphoma initially treated with chemotherapy--result of chemotherapy in NK/T-cell lymphoma. Acta Oncol. 2003;42(7):779-83. \u003c/li\u003e\n\u003cli\u003eLi YX, Yao B, Jin J, Wang WH, Liu YP, Song YW, et al. Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma. J Clin Oncol. 2006;24(1):181-9. \u003c/li\u003e\n\u003cli\u003eLee J, Suh C, Park YH, Ko YH, Bang SM, Lee JH, et al. Extranodal natural killer T-cell lymphoma, nasal-type: a prognostic model from a retrospective multicenter study. J Clin Oncol. 2006;24(4):612-8. \u003c/li\u003e\n\u003cli\u003eLiang R. Advances in the management and monitoring of extranodal NK/T-cell lymphoma, nasal type. Br J Haematol. 2009;147(1):13-21. \u003c/li\u003e\n\u003cli\u003eVose J, Armitage J, Weisenburger D, International TCLP. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124-30. \u003c/li\u003e\n\u003cli\u003eYamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, et al. Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211. J Clin Oncol. 2009;27(33):5594-600. \u003c/li\u003e\n\u003cli\u003eJaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, et al. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood. 2011;117(6):1834-9. \u003c/li\u003e\n\u003cli\u003eKim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, et al. Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell Lymphoma: Consortium for Improving Survival of Lymphoma study. J Clin Oncol. 2009;27(35):6027-32. \u003c/li\u003e\n\u003cli\u003eYamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, et al. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study. J Clin Oncol. 2011;29(33):4410-6. \u003c/li\u003e\n\u003cli\u003eKim SJ, Park S, Kang ES, Choi JY, Lim DH, Ko YH, et al. Induction treatment with SMILE and consolidation with autologous stem cell transplantation for newly diagnosed stage IV extranodal natural killer/T-cell lymphoma patients. Ann Hematol. 2015;94(1):71-8. \u003c/li\u003e\n\u003cli\u003eFox CP, Civallero M, Ko YH, Manni M, Skrypets T, Pileri S, et al. Survival outcomes of patients with extranodal natural-killer T-cell lymphoma: a prospective cohort study from the international T-cell Project. Lancet Haematol. 2020;7(4):e284-e94. \u003c/li\u003e\n\u003cli\u003eKim SJ, Yoon DH, Jaccard A, Chng WJ, Lim ST, Hong H, et al. A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis. Lancet Oncol. 2016;17(3):389-400. \u003c/li\u003e\n\u003cli\u003eYamaguchi M, Suzuki R, Miyazaki K, Amaki J, Takizawa J, Sekiguchi N, et al. Improved prognosis of extranodal NK/T cell lymphoma, nasal type of nasal origin but not extranasal origin. Ann Hematol. 2019;98(7):1647-55. \u003c/li\u003e\n\u003cli\u003eLee J, Au WY, Park MJ, Suzumiya J, Nakamura S, Kameoka J, et al. Autologous hematopoietic stem cell transplantation in extranodal natural killer/T cell lymphoma: a multinational, multicenter, matched controlled study. Biol Blood Marrow Transplant. 2008;14(12):1356-64. \u003c/li\u003e\n\u003cli\u003eWang H, Wang L, Li C, Wuxiao Z, Chen G, Luo W, et al. Pegaspargase Combined with Concurrent Radiotherapy for Early-Stage Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Two-Center Phase II Study. Oncologist. 2020;25(11):e1725-e31. \u003c/li\u003e\n\u003cli\u003eDong LH, Zhang LJ, Wang WJ, Lei W, Sun X, Du JW, et al. Sequential DICE combined with l-asparaginase chemotherapy followed by involved field radiation in newly diagnosed, stage IE to IIE, nasal and extranodal NK/T-cell lymphoma. Leuk Lymphoma. 2016;57(7):1600-6. \u003c/li\u003e\n\u003cli\u003eKwong YL, Kim SJ, Tse E, Oh SY, Kwak JY, Eom HS, et al. Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma. Ann Oncol. 2018;29(1):256-63. \u003c/li\u003e\n\u003cli\u003eJiang M, Zhang H, Jiang Y, Yang Q, Xie L, Liu W, et al. Phase 2 trial of \u0026quot;sandwich\u0026quot; L-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma. Cancer. 2012;118(13):3294-301. \u003c/li\u003e\n\u003cli\u003eZhang L, Jiang M, Xie L, Zhang H, Jiang Y, Yang QP, et al. Five-year analysis from phase 2 trial of \u0026quot;sandwich\u0026quot; chemoradiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma. Cancer Med. 2016;5(1):33-40. \u003c/li\u003e\n\u003cli\u003eKwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, et al. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012;120(15):2973-80. \u003c/li\u003e\n\u003cli\u003eGao Y, Huang H-q, QiChun C, Wang X, Cai Q, Xia Z, et al. Efficacy and Safety Of Pegaspargase With Gemcitabine and Oxaliplatin In Patients With Treatment-na\u0026iuml;ve, Refractory Extranodal Natural Killer/T-Cell Lymphoma: A Single-Centre Experience. Blood. 2013;122(21):642-. \u003c/li\u003e\n\u003cli\u003eJi J, Xiang B, Liu ZG, Jia YQ, Zhu HL, Niu T, et al. Efficacy of GLIDE chemotherapy for patients with newly diagnosed advanced-stage or relapsed/refractory extranodal natural killer cell lymphoma. Chin J Hematol. 2016;37(9):5. \u003c/li\u003e\n\u003cli\u003eJi J, Liu T, Xiang B, Liu W, He C, Chen X, et al. A study of gemcitabine, l-asparaginase, ifosfamide, dexamethasone and etoposide chemotherapy for newly diagnosed stage IV, relapsed or refractory extranodal natural killer/T-cell lymphoma, nasal type. Leuk Lymphoma. 2014;55(12):2955-7. \u003c/li\u003e\n\u003cli\u003eShen Z, Chen X, Sun C, Lu T, Shi Y, Zhang H, Ye J, Wang L, Zhu T, Miao Y, Zhang X, Wang L, Cai G, Sang W. Comparative analysis of clinicopathologic characteristics and prognosis between nasal and nonnasal extranodal NK/T-cell lymphoma. Cancer Med. 2023 Dec;12(23):21138-21147.\u003c/li\u003e\n\u003cli\u003eMontes-Mojarro IA, Chen BJ, Ramirez-Ibarguen AF, Quezada-Fiallos CM, P\u0026eacute;rez-B\u0026aacute;ez WB, Due\u0026ntilde;as D, Casavilca-Zambrano S, Ortiz-Mayor M, Rojas-Bilbao E, Garc\u0026iacute;a-Rivello H, Metrebian MF, Narbaitz M, Barrionuevo C, Lome-Maldonado C, Bonzheim I, Fend F, Steinhilber J, Quintanilla-Martinez L. Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America. Mod Pathol. 2020 May;33(5):781-791.\u003c/li\u003e\n\u003cli\u003eShen Z, Zhang S, Chen X, Zhang Q, Jiao Y, Shi Y, Zhang H, Ye J, Wang L, Zhu T, Miao Y, Wang L, Cai G, Sang W. Prognostic value of prognostic nutritional index on extranodal natural killer/T-cell lymphoma patients: A multicenter propensity score matched analysis of 1022 cases in Huaihai Lymphoma Working Group. Hematol Oncol. 2023 Aug;41(3):380-388. doi: 10.1002/hon.3124. Epub 2023 Jan 29. PMID: 36680513.\u003c/li\u003e\n\u003cli\u003eWang C, Bai H, Xi R, Pan Y, Xu S, Zhang Q, Chen Y, Zhou J. [Curative effect of nasal type extranodal NK/T-cell lymphoma by sequential chemotherapy combined radiotherapy compared with chemotherapy]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2013 Dec;27(23):1283-6, 1290.\u003c/li\u003e\n\u003cli\u003eYang CW, Wang CW, Hong RL, Tsai CL, Yao M, Tang JL, Lin CW, Cheng AL, Kuo SH. Treatment outcomes of and prognostic factors for definitive radiotherapy with and without chemotherapy for Stage I/II nasal extranodal NK/T-cell lymphoma. J Radiat Res. 2017 Jan;58(1):114-122.\u003c/li\u003e\n\u003cli\u003eYan Z, Yao S, Wang Z, Zhou W, Yao Z, Liu Y. Treatment of extranodal NK/T-cell lymphoma: From past to future. Front Immunol. 2023 Feb 7;14:1088685.\u003c/li\u003e\n\u003cli\u003eWei YC, Qi F, Zheng BM, Zhang CG, Xie Y, Chen B, Liu WX, Liu WP, Fang H, Qi SN, Zhang D, Chai Y, Li YX, Wang WH, Song YQ, Zhu J, Dong M. Intensive therapy can improve long-term survival in newly diagnosed, advanced-stage extranodal NK/T-cell lymphoma: A multi-institutional, real-world study. Int J Cancer. 2023 Nov 1;153(9):1643-1657.\u003c/li\u003e\n\u003cli\u003eChauchet A, Michallet AS, Berger F, Bedgedjian I, Deconinck E, Sebban C, Antal D, Orfeuvre H, Corront B, Petrella T, Hacini M, Bouteloup M, Salles G, Coiffier B. Complete remission after first-line radio-chemotherapy as predictor of survival in extranodal NK/T cell lymphoma. J Hematol Oncol. 2012 Jun 8;5:27.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eClinical characteristics and treatment details of 408 ENKTL patients (n=408)\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"113%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003eNasal-type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003eExtranasal- type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u003c/em\u003e\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e1.586\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.208\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026le;60 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e354 (86.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e298 (85.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e56 (91.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026gt;60 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e54 (13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e49 (14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5 (8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.652\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.420\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e266 (65.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e229 (66.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e37 (60.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e142 (34.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e118 (34.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e24 (39.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eB symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.423\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.120\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e198 (48.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e174 (50.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e24 (39.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e210 (51.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e173 (49.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e37 (60.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eECOG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e51.195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026lt;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e372 (91.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e331 (95.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e41 (67.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026ge;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e36 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e16 (4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e20 (32.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLDH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e42.488\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e＜250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e279(68.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e259(74.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e20(32.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e250-499\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e103(25.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e74(21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e29(47.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e500-749\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e15(3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e9(2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e6(9.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026ge;750\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e11(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e5(1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e6(9.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eAnn Arbor stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e98.175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eⅠ-Ⅱ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e290 (71.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e279 (80.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e11 (18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eⅢ-Ⅳ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e118 (28.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e68 (19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e50 (82.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003ePINK-E score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e73.529\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e75 (18.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e75 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e188 (46.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e178 (51.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e10 (16.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026ge;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e145 (35.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e94 (27.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e51 (83.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eBone marrow involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e5.322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e400 (98.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e343 (98.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e57 (93.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e8 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e4 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4 (6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eDistant lymph node involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e32.788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e358 (87.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e318 (91.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e40 (65.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e50 (12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e29 (8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e21 (34.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eFirst-line treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e94.719\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eRadiotherapy alone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e11(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e11(3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eChemotherapy alone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e93(22.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e57(16.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3(59.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eChemotherapy and radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e280(68.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e269(77.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e11(18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eChemotherapy and ASCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e24(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e10(2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e14(23.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eFirst-line treatment achieved CR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e8.748\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e158(38.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e124(35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e34(55.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e250(61.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e223(64.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e27(44.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eChemotherapy regimen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e24.840\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eL-asparaginase+, platinum+, gemcitabine-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e201(49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e184(53.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e17(27.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eL-asparaginase+, platinum-, gemcitabine+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e102(25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e74(21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e28(45.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eL-asparaginase+, platinum+, gemcitabine+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e64(15.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e54(15.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e10(16.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eL-asparaginase+, platinum-, gemcitabine-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e11(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e7(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e4(6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eL-asparaginase-, platinum+, gemcitabine+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e8(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e7(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e1(1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eL-asparaginase-, platinum+, gemcitabine-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e6(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e6(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eL-asparaginase-, platinum-, gemcitabine-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e4(1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e3(0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e1(1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eENKTL=extranodal natural killer T-cell lymphoma.ECOG=Eastern Cooperative Oncology Group. ASCT= autologous hematopoietic stem cell transplantation.LDH= lactate dehydrogenase. PINK= the prognostic index of natural killer Lymphoma\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;\u003c/strong\u003eUnivariate and multivariate analysis of overall survival in 408 patients with ENKTL\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"678\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eUnivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 209px;\"\u003e\n \u003cp\u003eMultivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eAge (\u0026gt;60 years /\u0026le;60 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e1.394(0.810-2.400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.231\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eGender (female / male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e0.897(0.573-1.402)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.633\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eNasal-type (yes/no)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e0.313(0.194-0.505)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eB symptoms (yes/no)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e2.769(1.738-4.414)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eECOG (\u0026ge;2/\u0026lt;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e6.268(3.784-10.384)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e2.728(1.563-4.761)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eLDH (＜250)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003e250-499\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e2.991(1.905-4.694)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003e500-749\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e3.179(1.256-8.050)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003e\u0026ge;750\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e4.172(1.494-11.653)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eAnn Arbor stage (Ⅲ-Ⅳ/Ⅰ-Ⅱ)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e3.796(2.482-5.804)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003ePINK-E score (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e1.585(0.724-3.470)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003e\u0026ge;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e4.855(2.295-10.270)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eBone marrow involvement\u0026nbsp;(yes/no)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e3.603(1.319-9.840)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eDistant lymph node involvement\u0026nbsp;(yes/no)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e2.414(1.399-4.165)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eFirst-line treatment (Chemotherapy alone)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eRadiotherapy alone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e11.107(1.525-80.923)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e0.146(0.020-1.088)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.060\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eChemotherapy and radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e1.697(0.233-12.361)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.602\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e0.303(0.184-0.501)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eChemotherapy and ASCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e3.731(0.459-30.332)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0.218\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e0.373(0.162-0.857)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 232px;\"\u003e\n \u003cp\u003eFirst-line treatment achieved CR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e0.412(0.269-0.631)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e0.565(0.364-0.877)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eHR: Hazard ratio.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Extranodal NK/T-cell lymphoma, Chemotherapy, Radiotherapy, Survival analysis, Real world study","lastPublishedDoi":"10.21203/rs.3.rs-5768765/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5768765/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAims\u003c/h2\u003e \u003cp\u003eTo investigate the long-term survival of extranodal NK/T-cell lymphoma (ENKTL) before the era of new drugs.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective real-world study enrolled patients with ENKTL at xx hospital between January, 2012 and December, 2017. Survival analysis and multivariate Cox proportional hazard regression analysis were performed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 408 patients with ENKTL, the 5-year overall survival (OS) was 75.3%, and 5-year progression-free survival (PFS) was 75.3%. Nasal type had significantly better 5-year OS (78.8%) and PFS (78.8%) compared to extranasal type (45.1% and 45.6%, respectively; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Early-stage patients had higher 5-year OS (84.5%) and PFS (91.2%) with chemotherapy plus radiotherapy compared to chemotherapy alone (56.7% and 85.9%, respectively; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Asparaginase-based regimens improved outcomes, especially in advanced stages. Achieving complete remission (CR) after first-line treatment significantly improved 5-year OS (81.9%) and PFS (82.0%). Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) (HR\u0026thinsp;=\u0026thinsp;2.728, 95%CI: 1.563\u0026ndash;4.761); type of first-line treatment, including chemotherapy and radiotherapy (HR\u0026thinsp;=\u0026thinsp;0.303, 95%CI: 0.184\u0026ndash;0.501), chemotherapy and ASCT (HR\u0026thinsp;=\u0026thinsp;0.373, 95%CI: 0.162\u0026ndash;0.857), and first-line treatment achieved CR (HR\u0026thinsp;=\u0026thinsp;0.565, 95%CI: 0.364\u0026ndash;0.877), were independent prognostic factors for patients\u0026rsquo; OS.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eDifferent treatment strategies might impact the long-term survival of patients with ENKTL before the era of new drugs. Chemotherapy combined with radiotherapy, asparaginase-based regimens, and achieving complete remission (CR) after first-line treatment are associated with improved outcomes, particularly in early-stage and advanced-stage patients. Moreover, ECOG performance status, type of first-line treatment were independent prognostic factors for OS.\u003c/p\u003e","manuscriptTitle":"Long-term survival of extranodal NK/T-cell lymphoma: a single-center real- world study of 408 cases in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-09 04:51:12","doi":"10.21203/rs.3.rs-5768765/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6abb5e6e-2187-41f5-9d9e-5994b3fef0aa","owner":[],"postedDate":"January 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-10T05:53:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-09 04:51:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5768765","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5768765","identity":"rs-5768765","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}