Long-term outcomes of 40 Gy CCRT with weekly cisplatin and systemic chemotherapy in limited-stage ENKTL

ABSTRACT: Radiotherapy (RT) is central in the management of limited-stage extranodal natural killer/T-cell lymphoma (ENKTL), nasal type. Although international guidelines recommend 50 to 56 Gy, emerging data suggest that reduced-dose RT with a radiosensitizer may provide comparable control with less toxicity. We evaluated the long-term outcomes of 40 Gy concurrent chemoradiotherapy (CCRT) followed by systemic chemotherapy. We retrospectively analyzed 155 patients newly diagnosed with limited-stage ENKTL treated at Samsung Medical Center between 2000 and 2023. All patients received 40 Gy in RT in 20 fractions with weekly cisplatin (30 mg/m2), followed by systemic chemotherapy. Clinical characteristics, treatment response, survival outcomes, and relapse patterns were assessed. The median age was 50 years, and 64.5% were male. Most patients (73.5%) had nasal-type disease, whereas 20.0% had combined nasal and nonnasal upper aerodigestive tract involvement. At a median follow-up of 73 months, the 5-year progression-free survival (PFS) and overall survival rates were 68.0% and 82.2%, respectively. Pretreatment Epstein-Barr virus DNA positivity correlated with inferior PFS (P = .043). Patients receiving CCRT plus chemotherapy had better PFS than those receiving CCRT alone (P = .004). Relapses occurred in 54 (34.8%) patients, predominantly at extranodal distant sites (21.3%), whereas the local control rate remained high (86.5%). Secondary malignancies developed in 3 patients. Median 22-item sinonasal outcome test score was 8, indicating minimal sinonasal symptom burden. A 40 Gy CCRT regimen followed by systemic chemotherapy achieved durable local control and favorable long-term survival in limited-stage ENKTL. The predominance of distant, rather than regional, relapse supports the feasibility of this reduced-dose CCRT strategy combined with systemic therapy.