METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.
FUNDING: Samsung Biomedical Research Institute.
METHODS AND MATERIALS: Between October 2007 and May 2016, 106 patients with untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiation therapy consisted of pelvic irradiation (total dose, 50 Gy in 25 fractions including central shielding), prophylactic paraortic regional irradiation (36-40 Gy in 20 fractions), and either high- or low-dose-rate intracavitary brachytherapy (ICBT) according to institutional practice. The planned point A dose was 21 to 28 Gy in 3 to 4 fractions for high-dose-rate ICBT and 40 to 41 Gy in 1 to 2 fractions for low-dose-rate ICBT. Five cycles of weekly cisplatin (40 mg/m2) were administered during the radiation therapy course.
RESULTS: A total of 106 patients were enrolled. Of these, 9 had major protocol violations and 2 did not receive treatment because of worsened general condition. Thus, 95 patients were evaluable. The median follow-up was 56 months. Of the 95 patients, 76 (80%) received 4 or 5 cycles of chemotherapy. Acute grade 3 leukopenia was observed in 20 of the patients (21%), and late grade 3 gastrointestinal toxicity was observed in 3%. The 2-year local control, progression-free survival, and overall survival rate for all patients were 96%, 78%, and 90%, respectively.
CONCLUSIONS: The results indicated that prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.