Cancer Res Treat.  2019 Oct;51(4):1557-1567. 10.4143/crt.2018.681.

Characteristics, Prognostic Factors, and Survival of Patients with NK/T-Cell Lymphoma of Non-upper Aerodigestive Tract: A 17-Year Single-Center Experience

• Liu ZL
• Bi XW
• Zhang XW
• Lei DX
• Liu PP
• Yang H
• Gao Y
• Jiang YX
• Jiang WQ
• Xia Y

• KMID: 2460604
• DOI: http://doi.org/10.4143/crt.2018.681

Abstract

PURPOSE
The extranodal natural killer (NK)/T-cell lymphoma (NKTCL) of non-upper aerodigestive tract (NUAT) was found to have clinical heterogeneity compared with NKTCL of the upper aerodigestive tract (UAT) in small scale studies. We conducted this study in a much larger cohort to analyze the clinical characteristics, prognostic factors, treatment modality, and clinical outcomes of patients with NUAT-NKTCL.
MATERIALS AND METHODS
From January 2001 to December 2017, a total of 757 NKTCL patients were identified and included in this study, including 92 NUAT-NKTCL patients (12.2%) and 665 UAT-NKTCLpatients (87.8%).
RESULTS
NUAT-NKTCL patients had relatively poorer performance status, more unfavorable prognostic factors, and more advanced stage, compared with UAT-NKTCL patients. The 5-year overall survival (OS) was 34.7% for NUAT-NKTCL, which was significantly worse than UAT-NKTCL (64.2%, p<0.001). The median OS duration was 30.9 months for NUAT-NKTCL. Multivariate analysis showed that presence with B symptoms and elevated serum lactate dehydrogenase independently predicted worse OS. International prognostic index score and prognostic index of natural killer lymphoma score still had prognostic values in NUAT-NKTCL, while the Ann Arbor system could not accurately predict the OS.
CONCLUSION
NUAT-NKTCL is a distinctive subtype of NKTCL in many aspects. Patients with NUAT-NKTCL have relatively poorer performance status, more unfavorable prognostic factors, more advanced stage, and poorer prognosis.

Keyword

Extranodal NK-T-Cell Lymphoma; Non-upper aerodigestive tract; Prognostic factors; Survival

MeSH Terms

Cohort Studies
Humans
L-Lactate Dehydrogenase
Lymphoma*
Lymphoma, Extranodal NK-T-Cell
Multivariate Analysis
Population Characteristics
Prognosis
L-Lactate Dehydrogenase

Figure

• 

  Fig. 1. Kaplan-Meier plots of overall survival (OS) (A) and progression-free survival (PFS) (B) for non-upper aerodigestive tract (NUAT)‒natural killer/T-cell lymphoma (NKTCL) and upper aerodigestive tract (UAT)-NKTCL. HR, hazard ratio; CI, confidence interval.

• 

  Fig. 2. Kaplan-Meier plots of overall survivals (OS) for non-upper aerodigestive tract–natural killer/T-cell lymphoma by the International Prognostic Index (IPI) score (A) and the Prognostic Index of Natural Killer Lymphoma (PINK) score (B). HR, hazard ratio; CI, confidence interval.

• 

  Fig. 3. Kaplan-Meier plots of overall survival (OS) (A) and progression-free survival (PFS) (B) for non-upper aerodigestive tract–natural killer/T-cell lymphoma (NKTCL) by Ann Arbor stage; and Kaplan-Meier plots of OS (C) and PFS (D) for upper aerodigestive tract–NKTCL by Ann Arbor stage. HR, hazard ratio; CI, confidence interval.

Reference

References

1. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016; 127:2375–90.

2. 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; 113:3931–7.

3. Kim TM, Lee SY, Jeon YK, Ryoo BY, Cho GJ, Hong YS, et al. Clinical heterogeneity of extranodal NK/T-cell lymphoma, nasal type: a national survey of the Korean Cancer Study Group. Ann Oncol. 2008; 19:1477–84.

4. Lim ST, Hee SW, Quek R, Lim LC, Yap SP, Loong EL, et al. Comparative analysis of extra-nodal NK/T-cell lymphoma and peripheral T-cell lymphoma: significant differences in clinical characteristics and prognosis. Eur J Haematol. 2008; 80:55–60.

5. Suzuki R, Suzumiya J, Yamaguchi M, Nakamura S, Kameoka J, Kojima H, et al. Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type. Ann Oncol. 2010; 21:1032–40.

6. Pongpruttipan T, Sukpanichnant S, Assanasen T, Wannakrairot P, Boonsakan P, Kanoksil W, et al. Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and alphabeta, gammadelta, and alphabeta/gammadelta T-cell origin: a comprehensive clinicopathologic and phenotypic study. Am J Surg Pathol. 2012; 36:481–99.

7. Jo JC, Yoon DH, Kim S, Lee BJ, Jang YJ, Park CS, et al. Clinical features and prognostic model for extranasal NK/T-cell lymphoma. Eur J Haematol. 2012; 89:103–10.

8. Li S, Feng X, Li T, Zhang S, Zuo Z, Lin P, et al. Extranodal NK/T-cell lymphoma, nasal type: a report of 73 cases at MD Anderson Cancer Center. Am J Surg Pathol. 2013; 37:14–23.

9. Bai B, Huang HQ, Cai QC, Fan W, Wang XX, Zhang X, et al. Predictive value of pretreatment positron emission tomography/computed tomography in patients with newly diagnosed extranodal natural killer/T-cell lymphoma. Med Oncol. 2013; 30:339.

10. Lee J, Park YH, Kim WS, Lee SS, Ryoo BY, Yang SH, et al. Extranodal nasal type NK/T-cell lymphoma: elucidating clinical prognostic factors for risk-based stratification of therapy. Eur J Cancer. 2005; 41:1402–8.

11. Kim GE, Lee SW, Chang SK, Park HC, Pyo HR, Kim JH, et al. Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck. Radiother Oncol. 2001; 61:261–9.

12. 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; 42:779–83.

13. Kim WS, Song SY, Ahn YC, Ko YH, Baek CH, Kim DY, et al. CHOP followed by involved field radiation: is it optimal for localized nasal natural killer/T-cell lymphoma? Ann Oncol. 2001; 12:349–52.

14. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32:3059–68.

15. Tse E, Kwong YL. How I treat NK/T-cell lymphomas. Blood. 2013; 121:4997–5005.

16. 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; 24:612–8.

17. Ren YL, Nong L, Zhang S, Zhao J, Zhang XM, Li T. Analysis of 142 Northern Chinese patients with peripheral T/NK-Cell lymphomas: subtype distribution, clinicopathologic features, and prognosis. Am J Clin Pathol. 2012; 138:435–47.

18. Huang JJ, Zhu YJ, Xia Y, Zhao W, Lin TY, Jiang WQ, et al. A novel prognostic model for extranodal natural killer/T-cell lymphoma. Med Oncol. 2012; 29:2183–90.

19. Cai Q, Luo X, Liang Y, Rao H, Fang X, Jiang W, et al. Fasting blood glucose is a novel prognostic indicator for extranodal natural killer/T-cell lymphoma, nasal type. Br J Cancer. 2013; 108:380–6.

20. Vose J, Armitage J, Weisenburger D; International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008; 26:4124–30.

21. 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; 17:389–400.

22. Chauchet A, Michallet AS, Berger F, Bedgedjian I, Deconinck E, Sebban C, et al. Complete remission after first-line radiochemotherapy as predictor of survival in extranodal NK/T cell lymphoma. J Hematol Oncol. 2012; 5:27.

23. Chim CS, Ma SY, Au WY, Choy C, Lie AK, Liang R, et al. Primary nasal natural killer cell lymphoma: long-term treatment outcome and relationship with the International Prognostic Index. Blood. 2004; 103:216–21.

24. 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; 24:181–9.

25. Wang H, Li YX, Wang WH, Jin J, Dai JR, Wang SL, et al. Mild toxicity and favorable prognosis of high-dose and extended involved-field intensity-modulated radiotherapy for patients with early-stage nasal NK/T-cell lymphoma. Int J Radiat Oncol Biol Phys. 2012; 82:1115–21.

26. Wang ZY, Li YX, Wang WH, Jin J, Wang H, Song YW, et al. Primary radiotherapy showed favorable outcome in treating extranodal nasal-type NK/T-cell lymphoma in children and adolescents. Blood. 2009; 114:4771–6.

27. Kim GE, Cho JH, Yang WI, Chung EJ, Suh CO, Park KR, et al. Angiocentric lymphoma of the head and neck: patterns of systemic failure after radiation treatment. J Clin Oncol. 2000; 18:54–63.

28. Kim K, Chie EK, Kim CW, Kim IH, Park CI. Treatment outcome of angiocentric T-cell and NK/T-cell lymphoma, nasal type: radiotherapy versus chemoradiotherapy. Jpn J Clin Oncol. 2005; 35:1–5.

29. 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; 14:1356–64.

30. Ai WZ, Chang ET, Fish K, Fu K, Weisenburger DD, Keegan TH. Racial patterns of extranodal natural killer/T-cell lymphoma, nasal type, in California: a population-based study. Br J Haematol. 2012; 156:626–32.