This study investigated the effects of miRNA-155 on malignant biological characteristics of NK/T-cell lymphoma cell lines and the possible mechanism. The expression of miRNA-155 was detected in lymphoma cell lines fro...This study investigated the effects of miRNA-155 on malignant biological characteristics of NK/T-cell lymphoma cell lines and the possible mechanism. The expression of miRNA-155 was detected in lymphoma cell lines from different sources (SNK-6, YTS, Jurkat and DOHH2) by real-time PCR. Lentiviral vectors (pLL3.7) that could overexpress or downexpress miRNA-155 were constructed. Recombinant lentiviral particles were prepared and purified, and their titers determined. The expression of miRNA-155 in the infected SNK-6 cells and the cell proliferation were detected by PCR and CCK-8, respectively. Flow cytometry was used to determine the apoptosis of infected SNK-6 cells. The target of miRNA155 was predicted from Targetscan website. The effect of miRNA155 on FOXO3a expression was examined by Western blotting. The results showed that among the human NK/T-cell lymphoma cell lines SNK-6, YTS, Jurkat and DOHH2, the expression of miRNA-155 was highest in SNK-6. The infection efficiency of the recombinant lentivirns in SNK-6 was more than 70% at multiplicity of infection (MOI) of 100. The expression of miRNA-155 was significantly increased in SNK-6 cells infected by lentivirus vectors with high expression of miRNA-155 (4 times higher than the control group), and profoundly decreased in those infected with lentivirnses with low expression of miRNA-155. The proliferation of letivirns-infected SNK-6 cells was decreased as the expression of miRNA-155 reduced. The apoptosis rate was increased with the reduction in the expression of miRNA-155. FOXO3a was found to be a possible target of miRNA155, as suggested by Targetscan website. Western blotting showed that the expression of FOXO3a was significantly elevated in SNK-6 cells with miRNA-155 inhibition. It was concluded that reduction in miRNA-155 expression can inhibit the proliferation of SNK-6 lymphoma cells and promote their apoptosis, which may be associated with regulation of FOXO3a gene.展开更多
Extranodal natural killer (NK)IT-cell lymphoma, nasal type (ENKTCL) is a rarely kind of non-Hodgkin lymphoma (NHL). It is much more frequent in Asian and Latin American countries than other part of the world. It...Extranodal natural killer (NK)IT-cell lymphoma, nasal type (ENKTCL) is a rarely kind of non-Hodgkin lymphoma (NHL). It is much more frequent in Asian and Latin American countries than other part of the world. It typically affects nasal cavity. In China, one of its endemically places, ENKTCL accounts for 74%-96% of nasal NHL. Patients with ENKTCL usually show a highly aggressive clinical course, and its etiology is unclear. However, it is already proved that ENKTCL is associated with Epstein-Barr virus (EBV) infection, regardless patients', ethnicity and areas. Some studies show that the risk will increase among several occupations, such as farmer, who are frequently exposure to pesticides and chemical solvent and risk can be cut down if taking some protective measures.展开更多
Objective:To compare the efficacy and safety of the novel SVILE regimen with the P-GemOx regimen in patients with newly diagnosed extranodal natural killer/T-cell lymphoma,nasal type(ND-ENKTL).Methods:From April 2015 ...Objective:To compare the efficacy and safety of the novel SVILE regimen with the P-GemOx regimen in patients with newly diagnosed extranodal natural killer/T-cell lymphoma,nasal type(ND-ENKTL).Methods:From April 2015 to July 2018,103 patients with ND-ENKTL were randomly assigned to SVILE(experimental group)or P-GemOx(control group)chemotherapy followed by radiotherapy and consolidation chemotherapy.The primary endpoint was the overall response rate after 3 cycles of chemotherapy,and secondary study endpoints were complete response(CR),progression-free survival(PFS),and overall survival(OS).Safety was also evaluated.Results:There were no significant differences in baseline characteristics in the experimentalvs.control groups.In experimental and control groups,respectively,the overall response rates were 91.7%vs.97.0%for stageI/II and 75.0%vs.72.2%for stage III/IV.The CR rates were 83.4%vs.97.0%for stage I/II and 68.8%vs.61.1%for stage III/IV.None of those differences were significant.There was no significant difference in PFS and OS between groups and between patients in stage I/II and stage III/IV.The 3-year PFS and OS in stage I/II were 88.3%vs.93.3%and 88.8%vs.97.0%,respectively.The 3-year PFS and OS in stage III/IV were 46.2%vs.65.7%and 68.8%vs.72.2%,respectively.The common adverse events were hematological toxicity,hepatotoxicity,and coagulation abnormalities,which were found to be reversible with supportive therapy.Conclusions:The novel SVILE regimen has comparable effects to those of P-GemOx in patients with ND-ENKTL and is well tolerated.SVILE is a therapeutic option for ND-ENKTL.展开更多
AIM To provide the overall spectrum of gastrosplenic fistula(GSF) occurring in lymphomas through a systematic review including a patient at our hospital.METHODS A comprehensive literature search was performed in the M...AIM To provide the overall spectrum of gastrosplenic fistula(GSF) occurring in lymphomas through a systematic review including a patient at our hospital.METHODS A comprehensive literature search was performed in the MEDLINE database to identify studies of GSF occurring in lymphomas. A computerized search of our institutional database was also performed. In all cases, we analyzed the clinicopathologic/radiologic features, treatment and outcome of GSF occurring in lymphomas. RESULTS A literature search identified 25 relevant studies with 26 patients. Our institutional data search added 1 patient. Systematic review of the total 27 cases revealed that GSF occurred mainly in diffuse, large B-cell lymphoma(n = 23), but also in diffuse, histiocytic lymphoma(n = 1), Hodgkin's lymphoma(n = 2), and NK/T-cell lymphoma(n = 1, our patient). The common clinical presentations are constitutional symptoms(n = 20) and abdominal pain(n = 17), although acute gastrointestinal bleeding(n = 6) and infection symptoms due to splenic abscess(n = 3) are also noted. In all patients, computed tomography scanning was very helpful for diagnosing GSF and for evaluating the lymphoma extent. GSF could occur either post-chemotherapy(n = 10) or spontaneously(n = 17). Surgical resection has been the most common treatment. Once patients have recovered from the acute illness status after undergoing surgery, their long-term outcome has been favorable. CONCLUSION This systematic review provides an overview of GSF occurring in lymphomas, and will be helpful in making physicians aware of this rare disease entity.展开更多
Primary testicular NK/T-cell lymphoma is an extremely rare entity progressed rapidly.The aim of this study was to examine clinical and pathological features of primary testicular NK/T-cell lymphoma and to investigate ...Primary testicular NK/T-cell lymphoma is an extremely rare entity progressed rapidly.The aim of this study was to examine clinical and pathological features of primary testicular NK/T-cell lymphoma and to investigate the effective diagnosis and prognosis.In this paper,the two cases of primary testicular NK/T-cell lymphoma were observed by light microscopy,immunohistochemistry and examined by in situ hybridization for Epstein-Barr Virus(EBV) DNA and the literatures were reviewed.The two patients respectively present with bilateral and right-side painless testicular enlargement.The morphology of neoplastic cells of case 1 were small to medium,tumor cells of case 2 were small,medium and large mixed.The tumor cells grew diffusely with irregular and distort nuclear,destructed the organizational structure of the normal testis,and damaged blood vessels,meanwhile,coagulation necrosis was exist.Immunohistochemical staining of neoplastic cells showed positive for CD45,CD2,CD56,CD3ε(cytoplasm staining pattern),CD45RO and Granzyme B,and negative for CD57,CD20,CD79α,CD30,CK,MPO,TdT,Bcl-2 and PLAP were negative.In addition,the EBV DNA was detected in the lymphoma by In situ hybridization.In conclusion,the expression of CD56,CD3ε,and Granzyme B associated proteins and EBV examination by in situ hybridization play a vital role in diagnosis and differential diagnosis of primary testicular NK/T-cell lymphoma.展开更多
Extranodal natural killer(NK)/T-cell lymphoma,nasal type,exhibits aggressive tumor behavior and carries a poor prognosis.Recently,lymphomatoid gastropathy with NK/T cell infiltration into gastric mucosa has been recog...Extranodal natural killer(NK)/T-cell lymphoma,nasal type,exhibits aggressive tumor behavior and carries a poor prognosis.Recently,lymphomatoid gastropathy with NK/T cell infiltration into gastric mucosa has been recognized as a pseudo-malignant disease which regresses without treatment.Because the conventional immunohistochemical criteria of lymphomatoid gastropathy is similar to that of extranodal NK/T-cell lymphoma nasal type,it is difficult to distinguish between the two conditions by histopathological evaluation only.Here,we report a rare case of lymphomatoid gastropathy in a 57-year-old female.Gastroendoscopy on routine check-up revealed elevated reddish lesions < 1 cm in diameter in the gastric fornix and body.Although repeat endoscopies at 1 and 6 mo later revealed no gastric lesions at any locations without any treatments,at 12 mo later gastric lymphomatoid lesions recurred at gastric fornix and body.Histological examination of endoscopic biopsy specimens at 12 mo showed atypical NK cell infiltration with CD3+,CD4-,CD5-,CD7+,CD8-,CD20-,CD30-,CD56+,CD79a-and T-cell-restricted intracellular antigen-1+ into gastric mucosa.After treatment for Helicobacter pylori(H.pylori) eradication,the lesions disappeared in all locations of the gastric fornix and body over the subsequent 12 mo.Here,we report a case of H.pylori-positive lymphomatoid gastropathy with massive NK-cell proliferation,and also review the literature concerning newly identified lymphomatoid gastropathy based on comparison of extra nodal NK/T-cell lymphoma nasal type.In any case,these lesions are evaluated with biopsy specimens,the possibility of this benign entity should be considered,and excessive treatment should be carefully avoided.Close follow-up for this case of lymphomatoid gastropathy is necessary to exclude any underlying malignancy.展开更多
Objective Nasal-type natural killer/T-cell lymphoma of Waldeyer's ring (WR-NK/TL) has different clinico- pathological characteristics from those of other subtypes of NK/T lymphoma; thus, the optimal treatment remai...Objective Nasal-type natural killer/T-cell lymphoma of Waldeyer's ring (WR-NK/TL) has different clinico- pathological characteristics from those of other subtypes of NK/T lymphoma; thus, the optimal treatment remains unclear. To find a more effective treatment model for WR-NK/TL, we conducted a single-center study of concurrent radiochemotherapy. Methods Forty-five patients with newly diagnosed stage IE to liE WR-NKTL were randomly divided into two groups. The 23 cases in the concurrent radiochemotherapy group were treated with three-dimensional conformal radiotherapy (48-52 Gy) and 2 courses of DICE (dexamethasone, ifosfamide, cisplatin, and etoposide) synchronous chemotherapy. The 22 cases in the radiotherapy group only received three-dimen- sional conformal radiotherapy (50-54 Gy). The primary end points were overall survival (OS), progression- free survival (PFS), and toxicity. Results The 1-, 3-, and 4-year OS and PFS rates were 95.5%, 65.6%, and 45.9%, and 86.4%, 56.0%, and 46.7% in the radiotherapy group, and 100%, 88.5%, and 88.5%, and 100%, 82.0%, and 73.8% in the concurrent radiochemotherapy group, respectively. The OS (P = 0.0477) and PFS rates (P = 0.0488) were higher in the concurrent radiochemotherapy group than in the radiotherapy group. The overall re- sponse rate was 100% in both the radiotherapy group [complete response (CR), 18 cases] and concurrent radiochemotherapy group (CR, 22 cases). The concurrent radiochemotherapy group had more severe side effects, especially grade 3 + 4 events, such as leukopenia, anorexia, and stomatitis. However, side effects benefiting from excellent oral care were endurable. Conclusion Radiotherapy plus concurrent DICE chemotherapy may be an effective and safe compre- hensive treatment for patients with WR-NKTL.展开更多
Background:Nasal-type extranodal natural killer/T-cell lymphoma(ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract.However,it is unclear whether the primary site...Background:Nasal-type extranodal natural killer/T-cell lymphoma(ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract.However,it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement.The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL.Methods:To develop a nomogram,we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011.The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index(C-index) and calibration curve.Results:The 5-year overall survival(OS) and progression-free survival(PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL(OS:68.2%vs.46.0%,P = 0.030;PFS:53.4%vs.26.6%,P = 0.010).The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage HE ENKTCL(OS:66.3%vs.59.2%,P = 0.003;PFS:51.4%vs.40.3%,P = 0.009).Multivariate analysis showed that age >60 years,ECOG performance status score >2,elevated lactate dehydrogenase(LDH) level,extranasal primary site,and regional lymph node involvement were significantly associated with lower 5-year OS rate;age >60 years,elevated LDH level,extra-nasal primary site,and regional lymph node involvement were significantly associated with lower 5-year PFS rate.The nomogram included the primary site and regional lymph node involvement based on multivariate analysis.The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates,and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634,respectively.Conclusions:The primary site and regional lymph node involvement are independent prognostic factors for earlystage ENKTCL treated with chemotherapy followed by definitive radiotherapy.展开更多
文摘This study investigated the effects of miRNA-155 on malignant biological characteristics of NK/T-cell lymphoma cell lines and the possible mechanism. The expression of miRNA-155 was detected in lymphoma cell lines from different sources (SNK-6, YTS, Jurkat and DOHH2) by real-time PCR. Lentiviral vectors (pLL3.7) that could overexpress or downexpress miRNA-155 were constructed. Recombinant lentiviral particles were prepared and purified, and their titers determined. The expression of miRNA-155 in the infected SNK-6 cells and the cell proliferation were detected by PCR and CCK-8, respectively. Flow cytometry was used to determine the apoptosis of infected SNK-6 cells. The target of miRNA155 was predicted from Targetscan website. The effect of miRNA155 on FOXO3a expression was examined by Western blotting. The results showed that among the human NK/T-cell lymphoma cell lines SNK-6, YTS, Jurkat and DOHH2, the expression of miRNA-155 was highest in SNK-6. The infection efficiency of the recombinant lentivirns in SNK-6 was more than 70% at multiplicity of infection (MOI) of 100. The expression of miRNA-155 was significantly increased in SNK-6 cells infected by lentivirus vectors with high expression of miRNA-155 (4 times higher than the control group), and profoundly decreased in those infected with lentivirnses with low expression of miRNA-155. The proliferation of letivirns-infected SNK-6 cells was decreased as the expression of miRNA-155 reduced. The apoptosis rate was increased with the reduction in the expression of miRNA-155. FOXO3a was found to be a possible target of miRNA155, as suggested by Targetscan website. Western blotting showed that the expression of FOXO3a was significantly elevated in SNK-6 cells with miRNA-155 inhibition. It was concluded that reduction in miRNA-155 expression can inhibit the proliferation of SNK-6 lymphoma cells and promote their apoptosis, which may be associated with regulation of FOXO3a gene.
文摘Extranodal natural killer (NK)IT-cell lymphoma, nasal type (ENKTCL) is a rarely kind of non-Hodgkin lymphoma (NHL). It is much more frequent in Asian and Latin American countries than other part of the world. It typically affects nasal cavity. In China, one of its endemically places, ENKTCL accounts for 74%-96% of nasal NHL. Patients with ENKTCL usually show a highly aggressive clinical course, and its etiology is unclear. However, it is already proved that ENKTCL is associated with Epstein-Barr virus (EBV) infection, regardless patients', ethnicity and areas. Some studies show that the risk will increase among several occupations, such as farmer, who are frequently exposure to pesticides and chemical solvent and risk can be cut down if taking some protective measures.
基金This study was supported by grants from Beijing Municipal Science&Technology Commission(Grant No.Z151100004015089).
文摘Objective:To compare the efficacy and safety of the novel SVILE regimen with the P-GemOx regimen in patients with newly diagnosed extranodal natural killer/T-cell lymphoma,nasal type(ND-ENKTL).Methods:From April 2015 to July 2018,103 patients with ND-ENKTL were randomly assigned to SVILE(experimental group)or P-GemOx(control group)chemotherapy followed by radiotherapy and consolidation chemotherapy.The primary endpoint was the overall response rate after 3 cycles of chemotherapy,and secondary study endpoints were complete response(CR),progression-free survival(PFS),and overall survival(OS).Safety was also evaluated.Results:There were no significant differences in baseline characteristics in the experimentalvs.control groups.In experimental and control groups,respectively,the overall response rates were 91.7%vs.97.0%for stageI/II and 75.0%vs.72.2%for stage III/IV.The CR rates were 83.4%vs.97.0%for stage I/II and 68.8%vs.61.1%for stage III/IV.None of those differences were significant.There was no significant difference in PFS and OS between groups and between patients in stage I/II and stage III/IV.The 3-year PFS and OS in stage I/II were 88.3%vs.93.3%and 88.8%vs.97.0%,respectively.The 3-year PFS and OS in stage III/IV were 46.2%vs.65.7%and 68.8%vs.72.2%,respectively.The common adverse events were hematological toxicity,hepatotoxicity,and coagulation abnormalities,which were found to be reversible with supportive therapy.Conclusions:The novel SVILE regimen has comparable effects to those of P-GemOx in patients with ND-ENKTL and is well tolerated.SVILE is a therapeutic option for ND-ENKTL.
文摘AIM To provide the overall spectrum of gastrosplenic fistula(GSF) occurring in lymphomas through a systematic review including a patient at our hospital.METHODS A comprehensive literature search was performed in the MEDLINE database to identify studies of GSF occurring in lymphomas. A computerized search of our institutional database was also performed. In all cases, we analyzed the clinicopathologic/radiologic features, treatment and outcome of GSF occurring in lymphomas. RESULTS A literature search identified 25 relevant studies with 26 patients. Our institutional data search added 1 patient. Systematic review of the total 27 cases revealed that GSF occurred mainly in diffuse, large B-cell lymphoma(n = 23), but also in diffuse, histiocytic lymphoma(n = 1), Hodgkin's lymphoma(n = 2), and NK/T-cell lymphoma(n = 1, our patient). The common clinical presentations are constitutional symptoms(n = 20) and abdominal pain(n = 17), although acute gastrointestinal bleeding(n = 6) and infection symptoms due to splenic abscess(n = 3) are also noted. In all patients, computed tomography scanning was very helpful for diagnosing GSF and for evaluating the lymphoma extent. GSF could occur either post-chemotherapy(n = 10) or spontaneously(n = 17). Surgical resection has been the most common treatment. Once patients have recovered from the acute illness status after undergoing surgery, their long-term outcome has been favorable. CONCLUSION This systematic review provides an overview of GSF occurring in lymphomas, and will be helpful in making physicians aware of this rare disease entity.
基金supported by a grant from the Foundation of Chongqing Medical University(No.XBYB2007085)
文摘Primary testicular NK/T-cell lymphoma is an extremely rare entity progressed rapidly.The aim of this study was to examine clinical and pathological features of primary testicular NK/T-cell lymphoma and to investigate the effective diagnosis and prognosis.In this paper,the two cases of primary testicular NK/T-cell lymphoma were observed by light microscopy,immunohistochemistry and examined by in situ hybridization for Epstein-Barr Virus(EBV) DNA and the literatures were reviewed.The two patients respectively present with bilateral and right-side painless testicular enlargement.The morphology of neoplastic cells of case 1 were small to medium,tumor cells of case 2 were small,medium and large mixed.The tumor cells grew diffusely with irregular and distort nuclear,destructed the organizational structure of the normal testis,and damaged blood vessels,meanwhile,coagulation necrosis was exist.Immunohistochemical staining of neoplastic cells showed positive for CD45,CD2,CD56,CD3ε(cytoplasm staining pattern),CD45RO and Granzyme B,and negative for CD57,CD20,CD79α,CD30,CK,MPO,TdT,Bcl-2 and PLAP were negative.In addition,the EBV DNA was detected in the lymphoma by In situ hybridization.In conclusion,the expression of CD56,CD3ε,and Granzyme B associated proteins and EBV examination by in situ hybridization play a vital role in diagnosis and differential diagnosis of primary testicular NK/T-cell lymphoma.
文摘Extranodal natural killer(NK)/T-cell lymphoma,nasal type,exhibits aggressive tumor behavior and carries a poor prognosis.Recently,lymphomatoid gastropathy with NK/T cell infiltration into gastric mucosa has been recognized as a pseudo-malignant disease which regresses without treatment.Because the conventional immunohistochemical criteria of lymphomatoid gastropathy is similar to that of extranodal NK/T-cell lymphoma nasal type,it is difficult to distinguish between the two conditions by histopathological evaluation only.Here,we report a rare case of lymphomatoid gastropathy in a 57-year-old female.Gastroendoscopy on routine check-up revealed elevated reddish lesions < 1 cm in diameter in the gastric fornix and body.Although repeat endoscopies at 1 and 6 mo later revealed no gastric lesions at any locations without any treatments,at 12 mo later gastric lymphomatoid lesions recurred at gastric fornix and body.Histological examination of endoscopic biopsy specimens at 12 mo showed atypical NK cell infiltration with CD3+,CD4-,CD5-,CD7+,CD8-,CD20-,CD30-,CD56+,CD79a-and T-cell-restricted intracellular antigen-1+ into gastric mucosa.After treatment for Helicobacter pylori(H.pylori) eradication,the lesions disappeared in all locations of the gastric fornix and body over the subsequent 12 mo.Here,we report a case of H.pylori-positive lymphomatoid gastropathy with massive NK-cell proliferation,and also review the literature concerning newly identified lymphomatoid gastropathy based on comparison of extra nodal NK/T-cell lymphoma nasal type.In any case,these lesions are evaluated with biopsy specimens,the possibility of this benign entity should be considered,and excessive treatment should be carefully avoided.Close follow-up for this case of lymphomatoid gastropathy is necessary to exclude any underlying malignancy.
基金Supported by grants from the Health Department Foundation of Sichuan Province,China(No.090156)the Science and Technology Bureau Foundation of Nanchong City from China(No.2060402)
文摘Objective Nasal-type natural killer/T-cell lymphoma of Waldeyer's ring (WR-NK/TL) has different clinico- pathological characteristics from those of other subtypes of NK/T lymphoma; thus, the optimal treatment remains unclear. To find a more effective treatment model for WR-NK/TL, we conducted a single-center study of concurrent radiochemotherapy. Methods Forty-five patients with newly diagnosed stage IE to liE WR-NKTL were randomly divided into two groups. The 23 cases in the concurrent radiochemotherapy group were treated with three-dimensional conformal radiotherapy (48-52 Gy) and 2 courses of DICE (dexamethasone, ifosfamide, cisplatin, and etoposide) synchronous chemotherapy. The 22 cases in the radiotherapy group only received three-dimen- sional conformal radiotherapy (50-54 Gy). The primary end points were overall survival (OS), progression- free survival (PFS), and toxicity. Results The 1-, 3-, and 4-year OS and PFS rates were 95.5%, 65.6%, and 45.9%, and 86.4%, 56.0%, and 46.7% in the radiotherapy group, and 100%, 88.5%, and 88.5%, and 100%, 82.0%, and 73.8% in the concurrent radiochemotherapy group, respectively. The OS (P = 0.0477) and PFS rates (P = 0.0488) were higher in the concurrent radiochemotherapy group than in the radiotherapy group. The overall re- sponse rate was 100% in both the radiotherapy group [complete response (CR), 18 cases] and concurrent radiochemotherapy group (CR, 22 cases). The concurrent radiochemotherapy group had more severe side effects, especially grade 3 + 4 events, such as leukopenia, anorexia, and stomatitis. However, side effects benefiting from excellent oral care were endurable. Conclusion Radiotherapy plus concurrent DICE chemotherapy may be an effective and safe compre- hensive treatment for patients with WR-NKTL.
文摘Background:Nasal-type extranodal natural killer/T-cell lymphoma(ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract.However,it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement.The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL.Methods:To develop a nomogram,we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011.The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index(C-index) and calibration curve.Results:The 5-year overall survival(OS) and progression-free survival(PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL(OS:68.2%vs.46.0%,P = 0.030;PFS:53.4%vs.26.6%,P = 0.010).The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage HE ENKTCL(OS:66.3%vs.59.2%,P = 0.003;PFS:51.4%vs.40.3%,P = 0.009).Multivariate analysis showed that age >60 years,ECOG performance status score >2,elevated lactate dehydrogenase(LDH) level,extranasal primary site,and regional lymph node involvement were significantly associated with lower 5-year OS rate;age >60 years,elevated LDH level,extra-nasal primary site,and regional lymph node involvement were significantly associated with lower 5-year PFS rate.The nomogram included the primary site and regional lymph node involvement based on multivariate analysis.The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates,and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634,respectively.Conclusions:The primary site and regional lymph node involvement are independent prognostic factors for earlystage ENKTCL treated with chemotherapy followed by definitive radiotherapy.