Shu‐Nan Qi

Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell's C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.

PURPOSE No randomized trials have compared hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) after breast-conserving surgery in the Asian population. This study aimed to determine whether a 3.5-week schedule of HFRT is noninferior to a standard 6-week schedule of CFRT in China. PATIENTS AND METHODS Patients from 4 Chinese institutions who had undergone breast-conserving surgery and had T1-2N0-3 invasive breast cancers participated this study. Patients were randomly assigned (1:1) using a computer-generated central randomization schedule, without stratification, to receive whole-breast irradiation with or without nodal irradiation, followed by tumor-bed boost, either at a dose of 50 Gy in 25 fractions over 5 weeks with a boost of 10 Gy in five fractions over 1 week (CFRT) or 43.5 Gy in 15 fractions over 3 weeks with a boost of 8.7 Gy in three daily fractions (HFRT). The primary endpoint was 5-year local recurrence (LR), and a 5% margin of 5-year LR was used to establish noninferiority. RESULTS Between August 2010 and November 2015, 734 patients were assigned to the HFRT (n = 368) or CFRT (n = 366) group. At a median follow-up of 73.5 months (interquartile range, 60.5-91.4 months), the 5-year cumulative incidence of LR was 1.2% in the HFRT group and 2.0% in the CFRT group (hazard ratio, 0.62; 95% CI, 0.20 to 1.88; P = .017 for noninferiority). There were no significant differences in acute and late toxicities, except that the HFRT group had less grade 2-3 acute skin toxicity than the CFRT group ( P = .019). CONCLUSION CFRT and HFRT with a tumor-bed boost may have similar low LR and toxicity.

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.