Background: Localized extranodal NK/T-cell lymphoma (ENKTL), nasal type, is commonly treated with radiotherapy (RT) and L-asparaginase (L-ASP) based chemotherapy. While international protocols often adopt RT doses of 50-56Gy, our center utilizes a low-dose RT strategy (40Gy in 20 fractions) with concurrent weekly cisplatin, followed by chemotherapy. This study aimed to evaluate long-term outcomes, relapse patterns, and the prognostic significance of EBV clearance in these patients under our protocol.

Methods: We retrospectively reviewed 155 patients with localized ENKTL treated between 1996 and 2022. All patients received RT (200cGy/day ⅹ20 fractions) with concurrent cisplatin (30mg/m2 weekly). Among them, 141 (91.0%) received subsequent chemotherapy (CCRT-CTX), and 14 (9.0%) received CCRT alone. Chemotherapy regimens included L-ASP-containing or non-L-ASP-based protocols. Outcomes were analyzed according to EBV status, treatment response, and relapse patterns. The incidence of secondary primary malignancies was also recorded.

Results: The median age was 50 (range, 15-82), and 64.5% were male. Most patients(65.2%) had stage IE, and 89.0% had involvement of the nasal cavity. 69.0% of patients were classified as PINK 0, and 85.8% as PINK-E 0-1. Of 141 (91.0%) patients who received CCRT-CTX, 85.8% presented CR. In the 14 patients treated with CCRT alone, 57.1% maintained CR. With a median follow-up of 73 months (range 62-83), the PFS was 142 months, and the OS had not been reached. Patients treated with CCRT-CTX had significantly longer PFS than those treated with CCRT alone (p=0.004). PFS and OS did not significantly differ by the type of chemotherapy regimen (VI DL, VIPD, MIDL, GDP) or L-ASP use. Post-treatment EBV DNA negativity was associated with a favorable trend toward improved PFS (p=0.092). However, when combined with treatment response, patients who achieved CR and EBV negativity had significantly better PFS (p<0.001) and OS (p=0.061) than those with non-CR or EBV positivity.

Of the 155 patients, 54 (34.8%) experienced relapse, including 29 at the primary site and 25 at distant sites. The primary site control rate was 81.3% (n=126/155) despite the use of low-dose RT (40Gy). Regarding long-term toxicity, the incidence of secondary malignancies was low (3 cases: breast cancer, melanoma, bladder cancer), suggesting that the limited RT field and low-dose strategy may reduce the risk of second cancers.

Conclusion: In localized ENKTL, a low-dose and limited RT approach with concurrent cisplatin showed favorable long-term outcomes with a low incidence of secondary malignancies. Additional chemotherapy after CCRT significantly improved survival. Post-treatment EBV negativity combined with CR was associated with a better prognosis and may serve as a practical prognostic marker. The outcome is relatively favorable compared to prior studies using high-dose RT, suggesting that RT dose de-escalation may be feasible in selected patients.

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2025
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