Failure patterns and clinical implications in early stage nasal natural killer/T‐cell lymphoma treated with primary radiotherapy

Abstract

BACKGROUND: This study aimed to evaluate the failure patterns and clinical implications in patients with early stage nasal natural killer (NK)/T-cell lymphoma treated with primary radiotherapy. METHODS: Two-hundred fourteen patients were included. There were 182 cases of stage I and 32 cases of stage II disease. Patients received radiotherapy alone (n ¼ 96) or radiotherapy and chemotherapy (n ¼ 118). The median dose was 50 grays, and most patients received doxorubicin-based chemotherapy. RESULTS: The 5-year overall survival (OS) and progression-free survival rates for all patients were 72% and 65%, respectively. Sixty-three patients experienced treatment failure. The 5-year cumulative incidences of locoregional, systemic, and overall failures were 12.0%, 25.5%, and 32.9%, respectively. Stage and paranasal extension were significant predictors for systemic failure. The 5-year cumulative incidence of systemic failure was 22.6% for stage I disease versus 42.7% for stage II disease (P < .001), and 16.9% for limited disease versus 30.4% for paranasal extension (P < .001), respectively. Adding chemotherapy to extended involved-field radiotherapy did not significantly decrease the systemic failure rate nor improve survival. The cumulative incidence of systemic failure and OS rate at 5 years were 24.1% and 74.4% for combined modality therapy compared with 28.5% (P ¼ 0.758) and 69.8% (P ¼ 0.529) for radiotherapy alone. A very low incidence of cervical lymph node or central nervous system relapse was observed. CONCLUSIONS: Patients with early stage nasal NK/T-cell lymphoma have excellent locoregional control and favorable prognosis with radiotherapy, but patients with stage II disease or paranasal extension are at high risk of systemic failure, emphasizing the importance of integration of optimal radiotherapy with innovative systemic therapy.

Current and future management of NK/T-cell lymphoma based on clinical trials

“…The two prospective trials of concurrent chemoradiotherapy [10,11] had not selected patients having risk factors. As shown in Table 2, the baseline clinical characteristics are comparable among the patients included in the two major recent retrospective studies of localized nasal NKTCL [47,48] and those enrolled in the two prospective clinical trials of concurrent chemoradiotherapy [10,11]. This similarity may be due to the median age at diagnosis and performance status of ENKL being lower than in other aggressive lymphomas, such as diffuse large B-cell lymphoma.…”

"Sandwich" Chemotherapy (CT) with Radiotherapy (RT) Improves Outcomes in Patients with Stage IE/IIEExtranodal Natural Killer (NK)/T-cell Lymphomas

“…An analysis of 102 patients treated with RT alone led to the local failure in 48 cases (47%) and the systemic failure in 28 cases (27%) (Koom et al, 2004). The 5-year cumulative incidence of overall failure is as high as 32.9% in a study of 182 cases receiving RT alone or RT and CT (Li et al, 2011). However, it is obviously low (13.33%~19.2%) for CCRT or CT as the initial treatment (Kim et al, 2009;Jiang et al, 2012), which is consistent with our results that the systemic and local failure rates were 18.2%, 5.8%, respectively.…”

“…At diagnosis, approximately 80% of cases are localized to the nasal and upper aero-digestive tract (Oshimi et al, 2005;Lee et al, 2006;Jo et al, 2012). The overall survival (OS) at 5 years is 49.5~72% (Lee et al, 2006;Ma et al, 2010;Li et al, 2011;Yamaguchi et al, 2012). Until now, there remains a lack of consensus on treatment of ENKTL and no therapy is considered standard (Kohrt et al, 2009).…”

“…RT has been taken as the primary treatment for early stage nasal ENKTL (Li et al, 2006;Wang et al, 2009; , 2012), but the systemic failure is seen in 21.9~27% of early-stage diseases treated with RT alone (Smalley et al 1988;Kim et al, 2000;Koom et al, 2004;Li et al, 2011), suggesting a role for CT added to RT for this highly aggressive lymphoma. Like hematological malignant diseases, ENKTL tends to disseminate many other tissues or organs (Chan et al, 1997).…”

Pediatric Natural Killer Cell Malignancy

“…A very low incidence of cervical lymph node or CNS relapse was observed. As a result, the addition of chemotherapy did not significantly decrease the systemic failure rate or improve survival [Li et al, 2011a]. In the Japanese JCOG 0211 study [Yamaguchi et al 2008], 27 patients received radiotherapy (50 Gy) and reduced-dose chemotherapy (carboplatin etoposide, ifosfamide, and dexamethasone).…”