Early-Stage Extranodal NK/T-Cell Lymphoma, Nasal Type: A Role for Elective Nodal Irradiation?

Abstract

Purpose: Extranodal NK/T-cell lymphoma (ENKTCL) is rare in the Western Hemisphere and is commonly treated with combined modality therapy (CMT).

Methods and materials: We retrospectively reviewed 35 patients treated with Ann Arbor stage I/II ENKTCL between 1994 and 2015 at a large academic cancer center in the United States.

Results: With 11.6 years median follow-up, median overall survival and progression-free survival were 13.5 and 7.5 years, respectively. Eighteen (51%) patients experienced disease relapse, with 5 regional nodal relapses, of which 2 experienced combined regional and distant relapses. All 5 regional nodal relapses occurred exclusively among patients not treated with elective nodal irradiation (ENI). ENI was associated with improved progression-free survival (hazard ratio [HR], 0.21; 95% CI, 0.09-0.52; P = .018) without significant association with OS (HR, 0.33; 95% CI, 0.11-0.94; P = .11). There was a trend toward improved local control with radiation dose to the primary tumor ≥50 Gy (HR, 0.29; 95% CI, 0.08-1.08; P = .098).

Conclusions: In this Western Hemisphere cohort of early-stage ENKTCL patients treated with CMT, ENI may have a potential clinical benefit, particularly in patients who are treated with non-asparaginase-containing CMT, such as in patients treated with radiation alone, patients treated with less intensive chemotherapy concurrently, or patients who are unable to tolerate intensive chemotherapy.

Figure 1

Progression-free survival (PFS) and overall survival (OS) for all patients with early-stage extranodal natural killer/T-cell lymphoma.

Figure 2

Progression-free survival (A) and overall survival (B) for all patients with early-stage extranodal natural killer/T-cell lymphoma who did and did not receive elective nodal irradiation (ENI).

Figure 3

Relapsed nodal disease in a patient with stage IIAE ENKTCL that was not treated with elective nodal irradiation. PET-CT images and the corresponding RT plan of a 65-year-old patient with ENKTCL involving the entire left nasal cavity (anterior and posterior involvement; a) and a 2.5 cm left level 1B submandibular lymph node without other nodal involvement identified (b, c). No other nodal sites of involvement were detected by PET-CT, MRI, or contrasted CT. The patient was planned to receive sequential therapy with upfront RT alone followed by systemic therapy. The patient was treated to 53.2 Gy in 28 fractions with volumetric modulated arc therapy to the sites of gross disease (contoured in red; d, e) and 47.6 Gy in 28 fractions to areas at risk for microscopic extension (contoured in blue; d, e). The patient did not receive elective nodal radiation to draining nodal basins. At the 3-month follow-up, the original sites of gross disease in the nasal cavity (g) and left submandibular region resolved (h); however, recurrent disease in other draining nodal basins including the right 1B submandibular region (h), the left facial nodal region (i), and the right retropharyngeal region (not shown) were identified despite not being present at diagnosis (b, c). This patient developed a second malignancy known as chondroblastic osteosarcoma within the left nasal cavity 8.3 years after completion of radiation. Abbreviations: CT = computed tomography; ENKTCL = extranodal natural killer/T-cell lymphoma; MRI = magnetic resonance imaging; PET = positron emission tomography; RT = radiation therapy.