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Original Investigation
January 2017

Association of Improved Locoregional Control With Prolonged Survival in Early-Stage Extranodal Nasal-Type Natural Killer/T-Cell Lymphoma

Author Affiliations
  • 1National Cancer Center, Beijing, PR China
  • 2Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China
  • 3Collaborative Innovation Center for Cancer Medicine, Beijing, PR China
  • 4Department of Radiation Oncology, Shanxi Cancer Hospital and the Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, Shanxi, PR China
  • 5Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, PR China
  • 6Department of Lymphoma, Guizhou Cancer Hospital, Guiyang, Guizhou, PR China
  • 7Department of Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan, PR China
  • 8Department of Radiation Oncology, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, PR China
  • 9Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China
  • 10Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, PR China
  • 11State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, PR China
  • 12Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, PR China
  • 13Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, PR China
  • 14Department of Radiation Oncology, Cancer Hospital, Tianjin Medical University, Tianjin, PR China
JAMA Oncol. 2017;3(1):83-91. doi:10.1001/jamaoncol.2016.5094
Key Points

Question  Does improved locoregional control translate into a survival benefit in patients with early-stage extranodal natural killer/T-cell lymphoma (NKTCL)?

Findings  In a cohort study of 1332 patients in China with early-stage NKTCL, radiotherapy had a dose-dependent association with locoregional control, progression-free survival, and overall survival. Improved locoregional control was associated with prolonged progression-free survival and overall survival.

Meaning  Clinicians and patients should be aware of the essential role of radiotherapy in both locoregional disease control and maintaining long-term survival.


Importance  The long-term survival benefit for radiotherapy (RT) in early-stage extranodal natural killer/T-cell lymphoma (NKTCL) is not known, and it is unclear whether improved locoregional control (LRC) translates into a survival benefit.

Objective  To investigate the dose-dependent effect and potential survival benefits of RT on the basis of LRC improvements.

Design, Setting, and Participants  Review of clinical data of patients with early-stage NKTCL at 10 institutions in China between 2000 and 2014. Radiotherapy dose as a continuous variable was entered into the Cox regression model by using penalized spline regression to allow for a nonlinear relationship between RT dose and events. Regression analysis was used to assess whether a linear correlation exists between LRC and progression-free survival (PFS) or overall survival (OS). Patients received chemotherapy (CT) alone, RT alone, or a combination. Chemotherapy alone was defined as 0 Gy.

Main Outcomes and Measures  The association between LRC and OS or PFS.

Results  A total of 1332 patients (923 [69%] male; median age, 43 years [range, 2-87 years]) were reviewed. For patients treated with RT, median dose was 50 Gy (range, 10-70 Gy); 996 (86%) received at least 50 Gy, and 164 (14%) received 10 to 49 Gy. The risk of locoregional recurrence, disease progression, and mortality decreased sharply until 50 to 52 Gy. For patients receiving RT, high-dose RT (≥50 Gy) was associated with significantly better 5-year LRC (85% vs 73%; P < .001), PFS (61% vs 50%; P = .004), and OS (70% vs 58%; P = .04) than low-dose RT (<50 Gy). Improved LRC with high-dose RT was independent of the RT/CT sequence or initial response to CT. Radiotherapy yielded a dose-dependent effect on LRC (range, 41%-87%), PFS (18%-63%), and OS (33%-71%). Dose-response regression analysis revealed a linear correlation between 5-year LRC and 5-year PFS (correlation coefficient, r = 0.994, P < .001; determination coefficient, R2 = 0.988) or 5-year OS (r = 0.985, P = .002; R2 = 0.97), which was externally validated using published data.

Conclusions and Relevance  The optimal dose was 50 Gy for patients with early-stage disease. The improved LRC was associated with prolonged survival. These findings emphasize the importance of RT in optimizing first-line therapy, and provide evidence for making treatment decisions and designing clinical trials.