Because of the low incidence of NK/T-cell malignancies, randomized control trials on treatment have not been available. Most treatment protocols are instead consensus based and are derived from retrospective and small prospective studies. The prognosis of nasal NK/T-cell lymphomas has gradually improved with modern treatment protocols combining chemotherapy and radiotherapy. On the other hand, prognosis remains guarded in most extranasal and disseminated cases.
For stage I/II nasal NK/T-cell lymphomas, radiotherapy is an important modality of treatment. Nonnasal NK cell lymphomas tend to have advanced or disseminated disease at presentation and the role of radiotherapy is often limited. The reported overall response rate of localized nasal disease after radiotherapy ranged from 60% to 80% with a complete remission (CR) rate of 40% 80% and a 5-year overall survival (OS) of 40 to 59% [13
]. Careful planning with the assistance of modern imaging modalities like CT and MRI is required before radiotherapy. A total radiotherapy dose of 30 to 60
Gy with fractional doses of 1.5 to 2.5
Gy is typically used [14
]. Despite the excellent initial response to radiotherapy alone, a high relapse rate of around 50% is reported. Local failure, including in-field and margin failures, usually occur within 1 year and is associated with a radiotherapy dose of less than 45 to 50
Gy and radiotherapy planning not assisted by imaging [23
]. Local relapses beyond 2 years are uncommon although late relapses have been reported [23
]. Systemic relapses occur in 25% to 30% of cases, more than half of which is not associated with local recurrences [13
]. In light of the high relapse rate with radiotherapy alone, combination of chemotherapy and radiotherapy is the current standard of care in patients who can tolerate systemic treatment. A commonly used anthracycline-containing regime is CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). Primary chemotherapy for stage I/II nasal NK/T-cell lymphomas yields a CR rate of around 40% to 60%. Nevertheless, a high rate of disease progression (30–40%) and relapse after initial CR (30–40%) is observed [13
]. The expression of multidrug resistance (MDR) gene and high levels of P-glycoprotein in NK lymphoma cells underlies the resistance to anthracyclines and vinca alkaloids [25
]. Regimens bases on non-P glycoprotein efflux chemotherapeutic agents such as L-asparaginase, ifosphamide, and methotrexate may potentially improve response rates. The optimal dose, combination and sequence of radiotherapy and chemotherapy remain to be defined though the current trend is to provide involved field radiotherapy after an initial three courses of chemotherapy. Concurrent chemoradiotherapy has been studied in two recent phase II trials with favorable results [26
]. In our center, for patients with stage I/II disease, the standard is to offer multiagent chemotherapy using the regimen SMILE (d
ethotrexate with leucovorin, i
-asparaginase, and e
toposide). A total of six courses of chemotherapy is offered. Involved-field radiation is administered after 3 courses of chemotherapy.