title: Association of Improved Locoregional Control With Prolonged Survival in Early-Stage Extranodal Nasal-Type Natural Killer/T-Cell Lymphoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: National Cancer Center, Beijing, PR China2Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China3Collaborative Innovation Center for Cancer Medicine, Beijing, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Shanxi Cancer Hospital and the Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Cao
authors.affiliation: Department of Radiation Oncology, Shanxi Cancer Hospital and the Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: Sheng-Min
authors.initials: SM
authors.lastname: Lan
authors.affiliation: Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, PR China.
authors.forename: Jun-Xin
authors.initials: JX
authors.lastname: Wu
authors.affiliation: Department of Lymphoma, Guizhou Cancer Hospital, Guiyang, Guizhou, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan, PR China.
authors.forename: Su-Yu
authors.initials: SY
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Qian
authors.affiliation: Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Hou
authors.affiliation: Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China.
authors.forename: Fu-Quan
authors.initials: FQ
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, PR China11State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, PR China12Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, PR China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Tianjin Medical University, Tianjin, PR China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Tianjin Medical University, Tianjin, PR China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yuan
authors.affiliation: National Cancer Center, Beijing, PR China2Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China3Collaborative Innovation Center for Cancer Medicine, Beijing, PR China.
authors.forename: Shu-Nan
authors.initials: SN
authors.lastname: Qi
authors.affiliation: National Cancer Center, Beijing, PR China2Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, PR China3Collaborative Innovation Center for Cancer Medicine, Beijing, PR China.
authors.forename: Ye-Xiong
authors.initials: YX
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002681:China; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D054391:Lymphoma, Extranodal NK-T-Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009367:Neoplasm Staging; D011829:Radiation Dosage