Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus-associated non-Hodgkin lymphoma with high incidence in Asia and Latin America. Approximately 70% of patients present with early-stage (I-II) disease confined to the upper aerodigestive tract. Radiotherapy at 50-56 Gy is the standard curative treatment, but high-dose radiotherapy causes severe toxicities including oral mucositis and xerostomia, while radiotherapy alone yields high systemic recurrence rates. Previous studies have confirmed the efficacy of P-GEMOX induction chemotherapy, verified the feasibility of reduced-dose radiotherapy in patients achieving complete response after chemotherapy, and demonstrated the radiosensitizing effect of selinexor via inhibiting IRF3-BARD1-BRCA1-mediated DNA damage repair. Moreover, international evidence supports the efficacy of 40 Gy radiotherapy combined with chemotherapy. Accordingly, this study hypothesizes that selinexor combined with 40 Gy reduced-dose radiotherapy following P-GEMOX induction chemotherapy can achieve equivalent efficacy to standard-dose radiotherapy, while markedly decreasing radiotherapy-related toxicities. This trial innovatively applies selinexor as a radiosensitizer in ENKTCL, fulfills the unmet clinical demand for efficacy-preserving toxicity reduction, and is well supported by preliminary data.
Aged 18 to 75 years, regardless of gender.
Pathologically confirmed extranodal NK/T-cell lymphoma (ENKTCL).
Ann Arbor stage I-II disease with primary lesion located in the nasal cavity or upper aerodigestive tract (UADT).
Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
Non-nasal type ENKTCL, or primary lesions outside the upper aerodigestive tract (UADT), including skin, gastrointestinal tract, lung and other sites.
Patients with Ann Arbor stage III-IV disease.
Central nervous system involvement.
History of prior malignant tumors, excluding non-melanoma skin cancer or cervical carcinoma in situ cured for more than 5 years.