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The optimal timing of radiotherapy in the combination treatment of limited-stage extranodal natural killer/T-cell lymphoma, nasal type: an updated meta-analysis

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Abstract

This study was designed to explore the relative efficacy and toxicity of upfront radiotherapy (RT) and late RT in combination treatments for patients with limited-stage extranodal natural killer/T-cell lymphoma nasal type (LS-ENKTL). We searched for clinical trials in the PubMed database that compared upfront RT with late RT in the combined treatment of patients with LS-ENKTL. We systematically evaluated the differences in survival, treatment response, and treatment-related adverse events (AEs) between these two groups. Ten retrospective studies with a total of 1752 patients were included. Upfront RT significantly prolonged the overall survival (OS) and progression-free survival (PFS) of patients compared to late RT in combination with chemotherapy (CT) (HR = 0.72, 95% CI 0.59–0.88, P = 0.001 for OS; HR = 0.57, 95% CI 0.41–0.79, P = 0.0007 for PFS). The complete remission (CR) rate in the upfront RT group was superior to that in the late RT group (HR = 1.61, 95% CI 1.09–2.37, P = 0.02). Patients experienced similar local recurrence-free survival (LRFS), objective response rates (ORR), and toxicity between these two arms (P > 0.05 for all) in the analysis of each subgroup. The survival benefit of upfront RT was not correlated with the RT dose, concurrent chemoradiotherapy (CCRT) (or not), or the CT regimen (P > 0.05 for all). Without compromises in terms of toxicity, RT dose, and treatment modality, upfront RT can significantly benefit OS, PFS, and CR compared to late RT in combination treatment. These findings verified that the upfront RT regimen is more suitable for patients with LS-ENKTL.

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References

  1. Yamaguchi M, Kita K, Miwa H et al (1995) Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells. Cancer 76:2351–2356

    Article  CAS  Google Scholar 

  2. Egashira M, Kawamata N, Sugimoto K et al (1999) P-glycoprotein expression on normal and abnormally expanded natural killer cells and inhibition of P-glycoprotein function by cyclosporin A and its analogue, PSC833. Blood 93:599–606

    Article  CAS  Google Scholar 

  3. Yamaguchi M, Suzuki R, Oguchi M (2018) Advances in the treatment of extranodal NK/T-cell lymphoma, nasal type. Blood 131:2528–2540

    Article  CAS  Google Scholar 

  4. Vargo JA, Patel A, Glaser SM et al (2017) The impact of the omission or inadequate dosing of radiotherapy in extranodal natural killer T-cell lymphoma, nasal type, in the United States. Cancer 123:3176–3185

    Article  CAS  Google Scholar 

  5. Li YX, Yao B, Jin J et al (2006) Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma. J Clin Oncol 24:181–189

    Article  Google Scholar 

  6. Lee J, Kim CY, Park YJ et al (2013) Sequential chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in patients with stage I/II extranodal natural killer/T-cell lymphoma, nasal type. Blood research 48:274–281

    Article  Google Scholar 

  7. Qian M, Tao H, Xu W et al (2017) A systematic comparison of treatment modalities for nasal extranodal natural killer/T-cell lymphoma in early stages between concurrent chemoradiotherapy and sequential chemotherapy. Onco Targets Ther 10:3617–3623

    Article  Google Scholar 

  8. Wang HY, Niu SQ, Yang YY et al (2018) Promising clinical outcomes of sequential and “Sandwich” chemotherapy and extended involved-field intensity-modulated radiotherapy in patients with stage I /II extranodal natural killer/T-cell lymphoma. Cancer Med 7:5863–5869

    Article  CAS  Google Scholar 

  9. Li J, Li Y, Zhong M et al (2018) A multicenter retrospective comparison of sequential versus sandwich chemoradiotherapy for stage IE-IIE extranodal natural killer/T-cell lymphoma, nasal type. J Cancer 9:1598–1606

    Article  Google Scholar 

  10. Kwong YL, Kim SJ, Tse E et al (2018) Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma. Ann Oncol 29:256–263

    Article  CAS  Google Scholar 

  11. Qi F, Chen B, Wang J et al (2019) Upfront radiation is essential for high-risk early-stage extranodal NK/T-cell lymphoma, nasal type: comparison of two sequential treatment modalities combining radiotherapy and GDP (gemcitabine, dexamethasone, and cisplatin) in the modern era. Leuk Lymphoma 60:2679–2688

    Article  CAS  Google Scholar 

  12. Tierney JF, Stewart LA, Ghersi D et al (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16

    Article  Google Scholar 

  13. Yang Y, Zhu Y, Cao JZ et al (2015) Risk-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma: analysis from a multicenter study. Blood 126:1424–1432

    Article  CAS  Google Scholar 

  14. Zang J, Li C, Luo SQ et al (2015) Early radiotherapy has an essential role for improving survival in patients with stage I-II nasal-type of NK/T cell lymphoma treated with L-asparaginase-containing chemotherapy–a single institution experience. Ann Hematol 94:583–591

    Article  CAS  Google Scholar 

  15. Kim TH, Kim JS, Suh YG et al (2016) The roles of radiotherapy and chemotherapy in the era of multimodal treatment for early-stage nasal-type extranodal natural killer/T-cell lymphoma. Yonsei Med J 57:846–854

    Article  CAS  Google Scholar 

  16. Moon JH, Lee BH, Kim JA et al (2016) Clinical impact of induction treatment modalities and optimal timing of radiotherapy for the treatment of limited-stage NK/T cell lymphoma. Leuk Res 49:80–87

    Article  Google Scholar 

  17. Liu XF, Wang X, Guo QS et al (2020) Clinical impact of the bolus in intensity-modulated radiotherapy and volumetric-modulated arc therapy for stage I-II nasal natural killer/T-cell lymphoma. Oncol Res Treat 43(4):140–145

    Article  CAS  Google Scholar 

  18. Dai GY, Xu X, Wu XH et al (2020) Application of 3D-print silica bolus for nasal NK/T-cell lymphoma radiation therapy. J Radiat Res 61(6):920–928

    Article  CAS  Google Scholar 

  19. Kim SJ, Yoon SE, Kim WS (2018) Treatment of localized extranodal NK/T cell lymphoma, nasal type: a systematic review. J Hematol Oncol 11:140

    Article  CAS  Google Scholar 

  20. Wu T, Yang Y, Zhu S et al (2018) Risk-adapted survival benefit of IMRT in early-stage NKTCL: a multicenter study from the China Lymphoma Collaborative Group. Blood Adv 2:2369–2377

    Article  CAS  Google Scholar 

  21. Deng XW, Wu JX, Wu T et al (2018) Radiotherapy is essential after complete response to asparaginase-containing chemotherapy in early-stage extranodal nasal-type NK/T-cell lymphoma: a multicenter study from the China Lymphoma Collaborative Group (CLCG). Radiother Oncol 129:3–9

    Article  Google Scholar 

  22. Isobe K, Uno T, Tamaru J et al (2006) Extranodal natural killer/T-cell lymphoma, nasal type: the significance of radiotherapeutic parameters. Cancer 106:609–615

    Article  Google Scholar 

  23. Yang Y, Cao JZ, Lan SM et al (2017) Association of improved locoregional control with prolonged survival in early-stage extranodal nasal-type natural killer/T-cell lymphoma. JAMA Oncol 3:83–91

    Article  Google Scholar 

  24. Qi S, Yahalom J, Hsu M et al (2016) Encouraging experience in the treatment of nasal type extra-nodal NK/T-cell lymphoma in a non-Asian population. Leuk Lymphoma 57:2575–2583

    Article  CAS  Google Scholar 

  25. Wang L, Bi X, Xia Z et al (2016) Radiation dose reduction for patients with extranodal NK/T-cell lymphoma with complete response after initial induction chemotherapy. Onco Targets Ther 9:5875–5881

    Article  CAS  Google Scholar 

  26. Wang L, Wang WD, Xia ZJ et al (2014) Combination of gemcitabine, L-asparaginase, and oxaliplatin (GELOX) is superior to EPOCH or CHOP in the treatment of patients with stage IE/IIE extranodal natural killer/T cell lymphoma: a retrospective study in a cohort of 227 patients with long-term follow-up. Med Oncol 31:860

    Article  Google Scholar 

  27. DE Felice F, Pranno N, Papi P et al (2020) VersusXerostomia and Clinical Outcomes in Definitive Intensity Modulated Radiotherapy (IMRT) Three-dimensional Conformal Radiotherapy (3D-CRT) for Head and Neck Squamous Cell Carcinoma: A Meta-analysis. In Vivo 34:623–629

    Article  Google Scholar 

  28. Shen Q, Ma X, Hu W et al (2013) Intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for stage I-II natural killer/T-cell lymphoma nasal type: dosimetric and clinical results. Radiat oncol 8:152

    Article  Google Scholar 

  29. Tomita N, Kodaira T, Tachibana H et al (2009) A comparison of radiation treatment plans using IMRT with helical tomotherapy and 3D conformal radiotherapy for nasal natural killer/T-cell lymphoma. Br J Radiol 82(981):756–763

    Article  Google Scholar 

  30. Hu S, Zhou D, Zhang W (2018) The optimal timing of radiotherapy in the combined modality therapy for limited-stage extranodal NK/T cell lymphoma (ENKTL): a systematic review and meta-analysis. Ann Hematol 97:2279–2287

    Article  CAS  Google Scholar 

  31. Qi SN, Li YQ, Specht L et al (2021) Modern radiation therapy for extranodal nasal-type NK/T-cell lymphoma: risk-adapted therapy, target volume, and dose guidelines from the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys 110(4):1064–1081

    Article  Google Scholar 

  32. Kim SJ, Kim K, Kim BS et al (2009) 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 27:6027–6032

    Article  CAS  Google Scholar 

  33. Huang M, Jiang Y, Liu W et al (2008) Early or up-front radiotherapy improved survival of localized extranodal NK/T-cell lymphoma, nasal-type in the upper aerodigestive tract. Int J Radiat Oncol Biol Phys 70:166–174

    Article  Google Scholar 

  34. Wu R, Liu K, Wang W et al (2017) Patterns of primary tumor invasion and regional lymph node spread based on magnetic resonance imaging in early-stage nasal NK/T-cell lymphoma: implications for clinical target volume definition and prognostic significance. Int J Radiat Oncol Biol Phys 97:50–59

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

    Yue Cui

  2. Department of Medical Oncology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, China

    Yuyi Yao & Meiting Chen

  3. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yongsheng Jiang & Quanguang Ren

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  1. Yue Cui
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  4. Yongsheng Jiang
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  5. Quanguang Ren
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Contributions

All the searches, including selecting titles, abstracts, and then the full texts of the correlative articles, were conducted by two investigators (Quanguang Ren, Yuyi Yao), independently; any disparities were solved by consensus or further turned to third senior participant (Yue Cui or Yongsheng Jiang); Cui and Ren wrote the main manuscript text; Yao, Meiting Chen, and Ren prepared the figures and tables.

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Correspondence to Yongsheng Jiang or Quanguang Ren.

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Yue Cui and Yuyi Yao contributed equally to this work as co-first authors.

Yongsheng Jiang and Quanguang Ren contributed equally to this work as co-corresponding authors

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Cui, Y., Yao, Y., Chen, M. et al. The optimal timing of radiotherapy in the combination treatment of limited-stage extranodal natural killer/T-cell lymphoma, nasal type: an updated meta-analysis. Ann Hematol 100, 2889–2900 (2021). https://doi.org/10.1007/s00277-021-04700-y

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