Radiotherapy alone versus combined therapy in stage I natural killer/T-cell lymphoma: impact of local invasion on treatment outcomes

Although combined modality therapy is frequently recommended for early-stage natural killer/T-cell lymphoma (NKTCL), the additional benefit of chemotherapy over radiation therapy (RT) alone in stage I disease remains unclear. We retrospectively analyzed 294 stage I NKTCL patients treated with RT with or without asparaginase-based chemotherapy across three centers in China and validated the findings in 242 patients from the SEER database. In the Chinese cohort, local invasion (defined as bone involvement, skin infiltration, perforation, or extension into the paranasal sinuses) and treatment modality were independent prognostic factors for progression-free survival (PFS) and overall survival (OS) (all P < 0.05). Chemotherapy plus RT significantly improved 5-year PFS (85.3% vs. 65.2%, P = 0.007) and OS (91.4% vs. 82.0%, P = 0.027) compared to RT alone. In subgroup analyses, patients without local invasion did not benefit from chemotherapy (5-year PFS: 91.9% vs. 87.6%, P = 0.19; 5-year OS: 96.4% vs. 96.3%, P = 0.55), whereas those with local invasion experienced substantial improvements (5-year PFS: 78.4% vs. 45.4%, P = 0.008; 5-year OS: 86.3% vs. 65.4%, P = 0.018). These findings were consistent after propensity score matching. In an exploratory analysis of the SEER cohort, chemotherapy improved OS among patients with primary involvement of non-nasal/nasopharyngeal sites (P = 0.044), but not in those with nasal/nasopharyngeal disease (P = 0.23). RT alone appears to provide excellent outcomes for stage I NKTCL without local invasion, while chemotherapy remains necessary for those with local invasion.