Risk-Dependent Conditional Survival and Failure Hazard After Radiotherapy for Early-Stage Extranodal Natural Killer/T-Cell Lymphoma
Authors: Xin Liu, Tao Wu, Su-Yu Zhu, Mei Shi, Hang Su, Ying Wang, Xia He, Li-Ming Xu, Zhi-Yong Yuan, Li-Ling Zhang, Gang Wu, Bao-Lin Qu, Li-Ting Qian, Xiao-Rong Hou, Fu-Quan Zhang, Yu-Jing Zhang, Yuan Zhu, Jian-Zhong Cao, Sheng-Min Lan, Jun-Xin Wu, Shu-Nan Qi, Yong Yang, Ye-Xiong Li
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Prognosis of early-stage extranodal natural killer/T-cell lymphoma (NKTCL) is usually estimated and stratified at diagnosis, but how the prognosis actually evolves over time for patients who survived after curative treatment is unknown. <h3>Objective</h3> To assess conditional survival and failure hazard over time based on risk categories, previous survival, and treatment. <h3>Design, Setting, and Participants</h3> This retrospective cohort study reviewed the clinical data of 2015 patients with early-stage NKTCL treated with radiotherapy identified from the China Lymphoma Collaborative Group multicenter database between January 1, 2000, and December 31, 2015. Patients were stratified into low-, intermediate- and high-risk groups according to a previously established prognostic model. Median follow-up was 61 months for surviving patients. Data analysis was performed from December 1, 2017, to January 30, 2018. <h3>Exposures</h3> All patients received radiotherapy with or without chemotherapy. <h3>Main Outcomes and Measures</h3> Conditional survival defined as the survival probability, given patients have survived for a defined time, and annual hazard rates defined as yearly event rate. <h3>Results</h3> A total of 2015 patients were included in the study (mean [SD] age, 43.3 [14.6] years; 1414 [70.2%] male); 1628 patients (80.8%) received radiotherapy with chemotherapy, and 387 (19.2%) received radiotherapy without chemotherapy. The 5-year survival rates increased from 69.1% (95% CI, 66.6%-71.4%) at treatment to 85.3% (95% CI, 81.7%-88.2%) at year 3 for conditional overall survival and from 60.9% (95% CI, 58.3%-63.3%) at treatment to 84.4% (95% CI, 80.6%-87.6%) at year 3 for conditional failure-free survival. The annual hazards decreased from 13.7% (95% CI, 13.0%-14.3%) for death and 22.1% (95% CI, 21.0%-23.1%) for failure at treatment to less than 5% after 3 years (death: range, 0%-3.9% [95% CI, 3.7%-4.2%]; failure: 1.2% [95% CI, 1.0%-1.4%] to 4.2% [95% CI 3.9%-4.6%]). Intermediate-risk (11.4% [95% CI, 10.5%-12.3%]) and high-risk (21.6% [95% CI, 20.0%-23.2%]) patients had initially higher but significantly decreased death hazards after 3 years (&lt;6%, range: 0%-5.9% [95% CI, 5.2%-6.7%]), whereas low-risk patients maintained a constantly lower death hazard of less than 5% (range, 0%-4.8%; 95% CI, 4.4%-5.3%). In high-risk patients, radiotherapy combined with non–anthracycline-based regimens were associated with higher conditional overall survival before year 3 compared with anthracycline-based regimens (hazard ratio [HR] for death, 1.49; 95% CI, 1.13-1.95;<i>P</i> = .004 at treatment; HR, 1.60; 95% CI, 1.07-2.39;<i>P</i> = .02 at 1 year; and HR, 1.77; 95% CI, 0.94-3.33;<i>P</i> = .07 at 2 years) or radiotherapy alone (HR, 2.42; 95% CI, 1.73-3.39;<i>P</i> &lt; .001 at treatment; HR, 1.82; 95% CI, 1.05-3.17;<i>P</i> = .03 at 1 year; and HR, 2.69; 95% CI, 1.23-5.90;<i>P</i> = .01 at 2 years). <h3>Conclusions and Relevance</h3> The survival probability increased and the hazards of failure decreased in a risk-dependent manner among patients with early NKTCL after radiotherapy. These dynamic data appear to provide accurate information on disease processes and continual survival expectations and may help researchers design additional prospective clinical trials and formulate risk-adapted therapies and surveillance strategies.